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Li Lan

Li Lan

Associate Professor of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
li.lan@duke.edu
424 CARL, Box 3054, Durham, NC 27710
424 CARL BX3054, 213 Reserch Drive, Durham, NC 27710

Selected Publications

ABL1-mediated tyrosine phosphorylation of SYCP2 contributes to transcription-coupled homologous recombination and platinum resistance in ovarian cancer.

Journal Article NAR Cancer · September 2025 Treatment of patients with platinum-resistant ovarian cancer is a major clinical challenge. We found that high expression of a meiotic protein, Synaptonemal Complex Protein 2 (SYCP2), is associated with platinum resistance and tyrosine kinase ABL1 inhibito ... Full text Open Access Link to item Cite

ZNF280A links DNA double-strand break repair to human 22q11.2 distal deletion syndrome.

Journal Article Nat Cell Biol · June 2025 DNA double-strand breaks (DSB) are among the most deleterious forms of DNA damage and, if unresolved, result in DNA mutations and chromosomal aberrations that can cause disease, including cancer. Repair of DSBs by homologous recombination requires extensiv ... Full text Link to item Cite

Transcription-coupled DNA repair protects genome stability upon oxidative stress-derived DNA strand breaks.

Journal Article FEBS Lett · January 2025 Elevated oxidative stress, which threatens genome stability, has been detected in almost all types of cancers. Cells employ various DNA repair pathways to cope with DNA damage induced by oxidative stress. Recently, a lot of studies have provided insights i ... Full text Link to item Cite

DSS1 restrains BRCA2's engagement with dsDNA for homologous recombination, replication fork protection, and R-loop homeostasis.

Journal Article Nat Commun · August 17, 2024 DSS1, essential for BRCA2-RAD51 dependent homologous recombination (HR), associates with the helical domain (HD) and OB fold 1 (OB1) of the BRCA2 DSS1/DNA-binding domain (DBD) which is frequently targeted by cancer-associated pathogenic variants. Herein, w ... Full text Link to item Cite

Revisiting Aurora Kinase B: A promising therapeutic target for cancer therapy.

Journal Article Med Res Rev · March 2024 Cancer continues to be a major health concern globally, although the advent of targeted therapy has revolutionized treatment options. Aurora Kinase B is a serine-threonine kinase that has been explored as an oncology therapeutic target for more than two de ... Full text Link to item Cite

Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair.

Journal Article Nat Commun · February 21, 2024 Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed ... Full text Link to item Cite

The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export.

Journal Article Cell Rep · January 23, 2024 Fanconi anemia (FA) is characterized by congenital abnormalities, bone marrow failure, and cancer susceptibility. The central FA protein complex FANCI/FANCD2 (ID2) is activated by monoubiquitination and recruits DNA repair proteins for interstrand crosslin ... Full text Link to item Cite

ATR inhibition induces synthetic lethality in mismatch repair-deficient cells and augments immunotherapy.

Journal Article Genes Dev · October 1, 2023 The mismatch repair (MMR) deficiency of cancer cells drives mutagenesis and offers a useful biomarker for immunotherapy. However, many MMR-deficient (MMR-d) tumors do not respond to immunotherapy, highlighting the need for alternative approaches to target ... Full text Link to item Cite

The RNA m5C modification in R-loops as an off switch of Alt-NHEJ.

Journal Article Nat Commun · September 30, 2023 The roles of R-loops and RNA modifications in homologous recombination (HR) and other DNA double-stranded break (DSB) repair pathways remain poorly understood. Here, we find that DNA damage-induced RNA methyl-5-cytosine (m5C) modification in R-loops plays ... Full text Link to item Cite

The DACH1 gene is frequently deleted in prostate cancer, restrains prostatic intraepithelial neoplasia, decreases DNA damage repair, and predicts therapy responses.

Journal Article Oncogene · June 2023 Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 si ... Full text Link to item Cite

Sources, resolution and physiological relevance of R-loops and RNA-DNA hybrids.

Journal Article Nat Rev Mol Cell Biol · August 2022 RNA-DNA hybrids are generated during transcription, DNA replication and DNA repair and are crucial intermediates in these processes. When RNA-DNA hybrids are stably formed in double-stranded DNA, they displace one of the DNA strands and give rise to a thre ... Full text Link to item Cite

FMRP promotes transcription-coupled homologous recombination via facilitating TET1-mediated m5C RNA modification demethylation.

Journal Article Proc Natl Acad Sci U S A · March 22, 2022 RNA modifications regulate a variety of cellular processes including DNA repair.The RNA methyltransferase TRDMT1 generates methyl-5-cytosine (m5C) on messen-ger RNA (mRNA) at DNA double-strand breaks (DSBs) in transcribed regions, pro-moting transcription- ... Full text Link to item Cite

DNA repair defects in cancer and therapeutic opportunities.

Journal Article Genes Dev · March 1, 2022 DNA repair and DNA damage signaling pathways are critical for the maintenance of genomic stability. Defects of DNA repair and damage signaling contribute to tumorigenesis, but also render cancer cells vulnerable to DNA damage and reliant on remaining repai ... Full text Link to item Cite

Immunostaining and Protein Pull-Down of Methyl-5-Cytosine-Marked RNA:DNA Hybrids.

Chapter · 2022 RNA:DNA hybrids not only function in various physiological cellular processes but also represent a threat to genome integrity. The methyl-5-cytosine (m5C) marked RNA:DNA hybrids containing the m5C modified RNA strand add another layer of regulation to the ... Full text Link to item Cite

RNA transcripts stimulate homologous recombination by forming DR-loops.

Journal Article Nature · June 2021 Homologous recombination (HR) repairs DNA double-strand breaks (DSBs) in the S and G2 phases of the cell cycle1-3. Several HR proteins are preferentially recruited to DSBs at transcriptionally active loci4-10, but how transcription promotes HR is poorly un ... Full text Link to item Cite

Alternative lengthening of telomeres is a self-perpetuating process in ALT-associated PML bodies.

Journal Article Mol Cell · March 4, 2021 Alternative lengthening of telomeres (ALT) is mediated by break-induced replication (BIR), but how BIR is regulated at telomeres is poorly understood. Here, we show that telomeric BIR is a self-perpetuating process. By tethering PML-IV to telomeres, we ind ... Full text Link to item Cite

Ubiquitination-mediated degradation of TRDMT1 regulates homologous recombination and therapeutic response.

Journal Article NAR Cancer · March 2021 The RNA methyltransferase TRDMT1 has recently emerged as a key regulator of homologous recombination (HR) in the transcribed regions of the genome, but how it is regulated and its relevance in cancer remain unknown. Here, we identified that TRDMT1 is poly- ... Full text Link to item Cite

cGAS suppresses genomic instability as a decelerator of replication forks.

Journal Article Sci Adv · October 2020 The cyclic GMP-AMP synthase (cGAS), a sensor of cytosolic DNA, is critical for the innate immune response. Here, we show that loss of cGAS in untransformed and cancer cells results in uncontrolled DNA replication, hyperproliferation, and genomic instabilit ... Full text Link to item Cite

An ordered assembly of MYH glycosylase, SIRT6 protein deacetylase, and Rad9-Rad1-Hus1 checkpoint clamp at oxidatively damaged telomeres.

Journal Article Aging (Albany NY) · September 29, 2020 In the base excision repair pathway, MYH/MUTYH DNA glycosylase prevents mutations by removing adenine mispaired with 8-oxoG, a frequent oxidative lesion. MYH glycosylase activity is enhanced by Rad9-Rad1-Hus1 (9-1-1) checkpoint clamp and SIRT6 histone/prot ... Full text Link to item Cite

The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2.

Journal Article Nucleic Acids Res · September 18, 2020 The NAD+-dependent deacetylase and mono-ADP-ribosyl transferase SIRT6 stabilizes the genome by promoting DNA double strand break repair, thereby acting as a tumor suppressor. However, whether SIRT6 regulates nucleotide excision repair (NER) remains unknown ... Full text Link to item Cite

m5C modification of mRNA serves a DNA damage code to promote homologous recombination.

Journal Article Nat Commun · June 5, 2020 Recruitment of DNA repair proteins to DNA damage sites is a critical step for DNA repair. Post-translational modifications of proteins at DNA damage sites serve as DNA damage codes to recruit specific DNA repair factors. Here, we show that mRNA is locally ... Full text Link to item Cite

Resolution of ROS-induced G-quadruplexes and R-loops at transcriptionally active sites is dependent on BLM helicase.

Journal Article FEBS Lett · May 2020 R-loops and G-quadruplexes (G4s) are noncanonical secondary DNA structures. Here, we show that reactive oxygen species (ROS) induce G4 formation as well as R-loops at transcriptionally active sites. Importantly, the G4 structure is subsequently triggered b ... Full text Link to item Cite

An R-loop-initiated CSB-RAD52-POLD3 pathway suppresses ROS-induced telomeric DNA breaks.

Journal Article Nucleic Acids Res · February 20, 2020 Reactive oxygen species (ROS) inflict multiple types of lesions in DNA, threatening genomic integrity. How cells respond to ROS-induced DNA damage at telomeres is still largely unknown. Here, we show that ROS-induced DNA damage at telomeres triggers R-loop ... Full text Link to item Cite

Cigarette smoke exposure enhances transforming acidic coiled-coil-containing protein 2 turnover and thereby promotes emphysema.

Journal Article JCI Insight · January 30, 2020 Our integrative genomic and functional analysis identified transforming acidic coiled-coil-containing protein 2 (TACC2) as a chronic obstructive pulmonary disease (COPD) candidate gene. Here, we found that smokers with COPD exhibit a marked decrease in lun ... Full text Link to item Cite

The DNA secondary structures at telomeres and genome instability.

Journal Article Cell Biosci · 2020 Telomeric DNA are TTAGGG tandem repeats, which are susceptible for oxidative DNA damage and hotspot regions for formation of DNA secondary structures such as t-loop, D-loop, G-quadruplexes (G4), and R-loop. In the past two decades, unique DNA or RNA second ... Full text Link to item Cite

Phosphatase 1 Nuclear Targeting Subunit Mediates Recruitment and Function of Poly (ADP-Ribose) Polymerase 1 in DNA Repair.

Journal Article Cancer Res · May 15, 2019 PARP, particularly PARP1, plays an essential role in the detection and repair of DNA single-strand breaks and double-strand breaks. PARP1 accumulates at DNA damage sites within seconds after DNA damage to catalyze the massive induction of substrate protein ... Full text Link to item Cite

Alternative Lengthening of Telomeres through Two Distinct Break-Induced Replication Pathways.

Journal Article Cell Rep · January 22, 2019 Alternative lengthening of telomeres (ALT) is a telomerase-independent but recombination-dependent pathway that maintains telomeres. Here, we describe an assay to visualize ALT-mediated telomeric DNA synthesis in ALT-associated PML bodies (APBs) without DN ... Full text Link to item Cite

Binding of FANCI-FANCD2 Complex to RNA and R-Loops Stimulates Robust FANCD2 Monoubiquitination.

Journal Article Cell Rep · January 15, 2019 Fanconi anemia (FA) is characterized by developmental abnormalities, bone marrow failure, and cancer predisposition. FA cells are hypersensitive to DNA replicative stress and accumulate co-transcriptional R-loops. Here, we use the Damage At RNA Transcripti ... Full text Link to item Cite

Localized protein biotinylation at DNA damage sites identifies ZPET, a repressor of homologous recombination.

Journal Article Genes Dev · January 1, 2019 Numerous DNA repair and signaling proteins function at DNA damage sites to protect the genome. Here, we show that fusion of the promiscuous biotin ligase BirAR118G with RAD18 leads to localized protein biotinylation at DNA damage sites, allowing identifica ... Full text Link to item Cite

Quantifying site-specific chromatin mechanics and DNA damage response.

Journal Article Sci Rep · December 27, 2018 DNA double-strand breaks pose a direct threat to genomic stability. Studies of DNA damage and chromatin dynamics have yielded opposing results that support either increased or decreased chromatin motion after damage. In this study, we independently measure ... Full text Link to item Cite

ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB.

Journal Article Nat Commun · October 8, 2018 Actively transcribed regions of the genome are protected by transcription-coupled DNA repair mechanisms, including transcription-coupled homologous recombination (TC-HR). Here we used reactive oxygen species (ROS) to induce and characterize TC-HR at a tran ... Full text Link to item Cite

SIRT6 facilitates directional telomere movement upon oxidative damage.

Journal Article Sci Rep · March 29, 2018 Oxidative damage to telomeres leads to telomere attrition and genomic instability, resulting in poor cell viability. Telomere dynamics contribute to the maintenance of telomere integrity; however, whether oxidative damage induces telomere movement and how ... Full text Link to item Cite

ELL2 regulates DNA non-homologous end joining (NHEJ) repair in prostate cancer cells.

Journal Article Cancer Lett · February 28, 2018 ELL2 is an androgen-responsive gene that is expressed by prostate epithelial cells and is frequently down-regulated in prostate cancer. Deletion of Ell2 in the murine prostate induced murine prostatic intraepithelial neoplasia and ELL2 knockdown enhanced p ... Full text Link to item Cite

RAD52 is required for RNA-templated recombination repair in post-mitotic neurons.

Journal Article J Biol Chem · January 26, 2018 It has been long assumed that post-mitotic neurons only utilize the error-prone non-homologous end-joining pathway to repair double-strand breaks (DSBs) associated with oxidative damage to DNA, given the inability of non-replicating neuronal DNA to utilize ... Full text Link to item Cite

POT1 inhibits the efficiency but promotes the fidelity of nonhomologous end joining at non-telomeric DNA regions.

Journal Article Aging (Albany NY) · December 8, 2017 Robust DNA double strand break (DSB) repair and stabilized telomeres help maintain genome integrity, preventing the onset of aging or tumorigenesis. POT1 is one of the six factors in the shelterin complex, which protects telomeres from being recognized as ... Full text Link to item Cite

Cleavage of Ku80 by caspase-2 promotes non-homologous end joining-mediated DNA repair.

Journal Article DNA Repair (Amst) · December 2017 Non-homologous end-joining (NHEJ)-mediated repair of DNA double-strand breaks (DSBs) requires the formation of a Ku70/Ku80/DNA-PKcs complex at the DSB sites. A previous study has revealed Ku80 cleavage by caspase-3 during apoptosis. However, it remains lar ... Full text Link to item Cite

Regulation of DNA break repair by transcription and RNA.

Journal Article Sci China Life Sci · October 2017 Repair of DNA double-strand breaks (DSBs) via the homologous recombination (HR) pathway is a highly regulated process. A number of proteins that participate in HR are intricately modulated by the cell cycle and chromatin environments of DSBs. Recent studie ... Full text Link to item Cite

The oxidative DNA damage response: A review of research undertaken with Tsinghua and Xiangya students at the University of Pittsburgh.

Journal Article Sci China Life Sci · October 2017 Endogenous stress and exogenous toxicants (chemicals and UV light) alter genetic information either directly or indirectly through the production of reactive oxygen species (ROS), thereby driving genomic instability in cells and promoting tumorigenesis. Al ... Full text Link to item Cite

An in situ-forming phospholipid-based phase transition gel prolongs the duration of local anesthesia for ropivacaine with minimal toxicity.

Journal Article Acta Biomater · August 2017 UNLABELLED: An injectable, phospholipid-based phase transition gel (PPTG) has been developed for prolonging the release of ropivacaine (RO) for local anesthesia. PPTG was prepared by mixing phospholipids, medium-chain triglyceride and ethanol. Prior to inj ... Full text Link to item Cite

SSRP1 Cooperates with PARP and XRCC1 to Facilitate Single-Strand DNA Break Repair by Chromatin Priming.

Journal Article Cancer Res · May 15, 2017 DNA single-strand breaks (SSB) are the most common form of DNA damage, requiring repair processes that to initiate must overcome chromatin barriers. The FACT complex comprised of the SSRP1 and SPT16 proteins is important for maintaining chromatin integrity ... Full text Link to item Cite

Tankyrase1-mediated poly(ADP-ribosyl)ation of TRF1 maintains cell survival after telomeric DNA damage.

Journal Article Nucleic Acids Res · April 20, 2017 Oxidative DNA damage triggers telomere erosion and cellular senescence. However, how repair is initiated at telomeres is largely unknown. Here, we found unlike PARP1-mediated Poly-ADP-Ribosylation (PARylation) at genomic damage sites, PARylation at telomer ... Full text Link to item Cite

WRN is recruited to damaged telomeres via its RQC domain and tankyrase1-mediated poly-ADP-ribosylation of TRF1.

Journal Article Nucleic Acids Res · April 20, 2017 Werner syndrome (WS) is a progeroid-like syndrome caused by WRN gene mutations. WS cells exhibit shorter telomere length compared to normal cells, but it is not fully understood how WRN deficiency leads directly to telomere dysfunction. By generating local ... Full text Link to item Cite

The Threshold Temperature and Lag Effects on Daily Excess Mortality in Harbin, China: A Time Series Analysis.

Journal Article Int J Occup Environ Med · April 2017 BACKGROUND: A large number of studies have reported the relationship between ambient temperature and mortality. However, few studies have focused on the effects of high temperatures on cardio-cerebrovascular diseases mortality (CCVDM) and their acute event ... Full text Link to item Cite

EAF2 regulates DNA repair through Ku70/Ku80 in the prostate.

Journal Article Oncogene · April 2017 Androgens are known to protect prostate cancer cells from DNA damage. Recent studies showed regulation of DNA repair genes by androgen receptor signaling in prostate cancers. ELL-associated factor 2 (EAF2) is an androgen-regulated tumor suppressor and its ... Full text Link to item Cite

Nek7 Protects Telomeres from Oxidative DNA Damage by Phosphorylation and Stabilization of TRF1.

Journal Article Mol Cell · March 2, 2017 Telomeric repeat binding factor 1 (TRF1) is essential to the maintenance of telomere chromatin structure and integrity. However, how telomere integrity is maintained, especially in response to damage, remains poorly understood. Here, we identify Nek7, a me ... Full text Link to item Cite

Induction of Site-Specific Oxidative Damage at Telomeres by Killerred-Fused Shelretin Proteins.

Chapter · 2017 Chronic oxidative stress is the major endogenous metabolic stress and contributes directly to telomere shortening and senescence. Understanding the dysfunction of telomeres under oxidative stress will greatly facilitate healthy aging and advance the treatm ... Full text Link to item Cite

Transcription-coupled homologous recombination after oxidative damage.

Journal Article DNA Repair (Amst) · August 2016 Oxidative DNA damage induces genomic instability and may lead to mutagenesis and carcinogenesis. As severe blockades to RNA polymerase II (RNA POLII) during transcription, oxidative DNA damage and the associated DNA strand breaks have a profoundly deleteri ... Full text Link to item Cite

The Lys63-deubiquitylating Enzyme BRCC36 Limits DNA Break Processing and Repair.

Journal Article J Biol Chem · July 29, 2016 Multisubunit protein assemblies offer integrated functionalities for efficient cell signal transduction control. One example of such protein assemblies, the BRCA1-A macromolecular complex, couples ubiquitin recognition and metabolism and promotes cellular ... Full text Link to item Cite

Guarding chromosomes from oxidative DNA damage to the very end.

Journal Article Acta Biochim Biophys Sin (Shanghai) · July 2016 The ends of each chromosome are capped by the telomere assembly to protect chromosomal integrity from telomere attrition and DNA damage. In response to DNA damage, DNA repair factors are enriched at damage sites by a sophisticated signaling and recruitment ... Full text Link to item Cite

Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis.

Journal Article Nat Commun · September 30, 2015 KLF4 is an important regulator of cell-fate decision, including DNA damage response and apoptosis. We identify a novel interplay between protein modifications in regulating KLF4 function. Here we show that arginine methylation of KLF4 by PRMT5 inhibits KLF ... Full text Link to item Cite

Fast and Precise 3D Fluorophore Localization based on Gradient Fitting.

Journal Article Sci Rep · September 22, 2015 Astigmatism imaging approach has been widely used to encode the fluorophore's 3D position in single-particle tracking and super-resolution localization microscopy. Here, we present a new high-speed localization algorithm based on gradient fitting to precis ... Full text Link to item Cite

Regulation of DNA Damage Signaling and Cell Death Responses by Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) and LMP2A in Nasopharyngeal Carcinoma Cells.

Journal Article J Virol · August 2015 UNLABELLED: Nasopharyngeal carcinoma (NPC) is closely associated with latent Epstein-Barr virus (EBV) infection. Although EBV infection of preneoplastic epithelial cells is not immortalizing, EBV can modulate oncogenic and cell death mechanisms. The viral ... Full text Link to item Cite

Targeted DNA damage at individual telomeres disrupts their integrity and triggers cell death.

Journal Article Nucleic Acids Res · July 27, 2015 Cellular DNA is organized into chromosomes and capped by a unique nucleoprotein structure, the telomere. Both oxidative stress and telomere shortening/dysfunction cause aging-related degenerative pathologies and increase cancer risk. However, a direct conn ... Full text Link to item Cite

DNA damage during the G0/G1 phase triggers RNA-templated, Cockayne syndrome B-dependent homologous recombination.

Journal Article Proc Natl Acad Sci U S A · July 7, 2015 Damage repair mechanisms at transcriptionally active sites during the G0/G1 phase are largely unknown. To elucidate these mechanisms, we introduced genome site-specific oxidative DNA damage and determined the role of transcription in repair factor assembly ... Full text Link to item Cite

ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors.

Journal Article Cancer Discov · July 2015 UNLABELLED: ARID1A, SWI/SNF chromatin remodeling complex subunit, is a recently identified tumor suppressor that is mutated in a broad spectrum of human cancers. Thus, it is of fundamental clinical importance to understand its molecular functions and deter ... Full text Link to item Cite

SIRT6 protein deacetylase interacts with MYH DNA glycosylase, APE1 endonuclease, and Rad9-Rad1-Hus1 checkpoint clamp.

Journal Article BMC Mol Biol · June 11, 2015 BACKGROUND: SIRT6, a member of the NAD(+)-dependent histone/protein deacetylase family, regulates genomic stability, metabolism, and lifespan. MYH glycosylase and APE1 are two base excision repair (BER) enzymes involved in mutation avoidance from oxidative ... Full text Link to item Cite

Differential phosphorylation of DNA-PKcs regulates the interplay between end-processing and end-ligation during nonhomologous end-joining.

Journal Article Mol Cell · April 2, 2015 Nonhomologous end-joining (NHEJ) is a major DNA double-strand break repair pathway that is conserved in eukaryotes. In vertebrates, NHEJ further acquires end-processing capacities (e.g., hairpin opening) in addition to direct end-ligation. The catalytic su ... Full text Link to item Cite

Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway.

Journal Article Nat Commun · February 11, 2015 Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand breaks (DSBs), which can display different types of broken ends. However, it is unclear how NHEJ factors organize to repair diverse types of DNA breaks. Here, through systemat ... Full text Link to item Cite

Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response.

Journal Article Cell Res · February 2015 Ataxia telangiectasia mutated (ATM) mediates DNA damage response by controling irradiation-induced foci formation, cell cycle checkpoint, and apoptosis. However, how upstream signaling regulates ATM is not completely understood. Here, we show that upon irr ... Full text Link to item Cite

RAD6 promotes homologous recombination repair by activating the autophagy-mediated degradation of heterochromatin protein HP1.

Journal Article Mol Cell Biol · January 2015 Efficient DNA double-strand break (DSB) repair is critical for the maintenance of genome stability. Unrepaired or misrepaired DSBs cause chromosomal rearrangements that can result in severe consequences, such as tumorigenesis. RAD6 is an E2 ubiquitin-conju ... Full text Link to item Cite

HSP90 regulates DNA repair via the interaction between XRCC1 and DNA polymerase β.

Journal Article Nat Commun · November 26, 2014 Cellular DNA repair processes are crucial to maintain genome stability and integrity. In DNA base excision repair, a tight heterodimer complex formed by DNA polymerase β (Polβ) and XRCC1 is thought to facilitate repair by recruiting Polβ to DNA damage site ... Full text Link to item Cite

Novel method for site-specific induction of oxidative DNA damage reveals differences in recruitment of repair proteins to heterochromatin and euchromatin.

Journal Article Nucleic Acids Res · February 2014 Reactive oxygen species (ROS)-induced DNA damage is repaired by the base excision repair pathway. However, the effect of chromatin structure on BER protein recruitment to DNA damage sites in living cells is poorly understood. To address this problem, we de ... Full text Link to item Cite

Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein.

Journal Article Nucleic Acids Res · February 2014 MUS81-EME1 is a DNA endonuclease involved in replication-coupled repair of DNA interstrand cross-links (ICLs). A prevalent hypothetical role of MUS81-EME1 in ICL repair is to unhook the damage by incising the leading strand at the 3' side of an ICL lesion. ... Full text Link to item Cite

A chemical probe targets DNA 5-formylcytosine sites and inhibits TDG excision, polymerases bypass, and gene expression

Journal Article Chemical Science · February 1, 2014 Dynamic regulation and faithful maintenance of proper DNA methylation patterns are essential for many cellular functions. 5-Formylcytosine (5fC), a newly discovered oxidized form of methylcytosine (mC), is involved in active DNA demethylation processes. Th ... Full text Cite

Ubiquitin-specific protease 5 is required for the efficient repair of DNA double-strand breaks.

Journal Article PLoS One · 2014 During the DNA damage response (DDR), ubiquitination plays an important role in the recruitment and regulation of repair proteins. However, little is known about elimination of the ubiquitination signal after repair is completed. Here we show that the ubiq ... Full text Link to item Cite

Damage response of XRCC1 at sites of DNA single strand breaks is regulated by phosphorylation and ubiquitylation after degradation of poly(ADP-ribose).

Journal Article J Cell Sci · October 1, 2013 Single-strand breaks (SSBs) are the most common type of oxidative DNA damage and they are related to aging and many genetic diseases. The scaffold protein for repair of SSBs, XRCC1, accumulates at sites of poly(ADP-ribose) (pAR) synthesized by PARP, but it ... Full text Link to item Cite

Monoubiquitinated histone H2A destabilizes photolesion-containing nucleosomes with concomitant release of UV-damaged DNA-binding protein E3 ligase.

Journal Article J Biol Chem · April 6, 2012 How the nucleotide excision repair (NER) machinery gains access to damaged chromatinized DNA templates and how the chromatin structure is modified to promote efficient repair of the non-transcribed genome remain poorly understood. The UV-damaged DNA-bindin ... Full text Link to item Cite

BRCA1 contributes to transcription-coupled repair of DNA damage through polyubiquitination and degradation of Cockayne syndrome B protein.

Journal Article Cancer Sci · October 2011 BRCA1 is an important gene involved in susceptibility to breast and ovarian cancer and its product regulates the cellular response to DNA double-strand breaks. Here, we present evidence that BRCA1 also contributes to the transcription-coupled repair (TCR) ... Full text Link to item Cite

Mutant Cockayne syndrome group B protein inhibits repair of DNA topoisomerase I-DNA covalent complex.

Journal Article Genes Cells · January 2011 Two UV-sensitive syndrome patients who have mild photosensitivity without detectable somatic abnormalities lack detectable Cockayne syndrome group B (CSB) protein because of a homozygous null mutation in the CSB gene. In contrast, mutant CSB proteins are p ... Full text Link to item Cite

The ACF1 complex is required for DNA double-strand break repair in human cells.

Journal Article Mol Cell · December 22, 2010 DNA double-strand breaks (DSBs) are repaired via nonhomologous end-joining (NHEJ) or homologous recombination (HR), but cellular repair processes remain elusive. We show here that the ATP-dependent chromatin-remodeling factors, ACF1 and SNF2H, accumulate r ... Full text Link to item Cite

Computerized assessment of breast lesion malignancy using DCE-MRI robustness study on two independent clinical datasets from two manufacturers.

Journal Article Acad Radiol · July 2010 RATIONALE AND OBJECTIVES: To conduct a preclinical evaluation of the robustness of our computerized system for breast lesion characterization on two breast magnetic resonance imaging (MRI) databases that were acquired using scanners from two different manu ... Full text Link to item Cite

DNA polymerase beta-dependent long patch base excision repair in living cells.

Journal Article DNA Repair (Amst) · February 4, 2010 We examined a role for DNA polymerase beta (Pol beta) in mammalian long patch base excision repair (LP BER). Although a role for Pol beta is well known in single-nucleotide BER, information on this enzyme in the context of LP BER has been limited. To exami ... Full text Link to item Cite

Rapid recruitment of BRCA1 to DNA double-strand breaks is dependent on its association with Ku80.

Journal Article Mol Cell Biol · December 2008 BRCA1 is the first susceptibility gene to be linked to breast and ovarian cancers. Although mounting evidence has indicated that BRCA1 participates in DNA double-strand break (DSB) repair pathways, its precise mechanism is still unclear. Here, we analyzed ... Full text Link to item Cite

Recruitment of mismatch repair proteins to the site of DNA damage in human cells.

Journal Article J Cell Sci · October 1, 2008 Mismatch repair (MMR) proteins contribute to genome stability by excising DNA mismatches introduced by DNA polymerase. Although MMR proteins are also known to influence cellular responses to DNA damage, how MMR proteins respond to DNA damage within the cel ... Full text Link to item Cite

A polycomb group protein, PHF1, is involved in the response to DNA double-strand breaks in human cell.

Journal Article Nucleic Acids Res · May 2008 DNA double-strand breaks (DSBs) represent the most toxic DNA damage arisen from endogenous and exogenous genotoxic stresses and are known to be repaired by either homologous recombination or nonhomologous end-joining processes. Although many proteins have ... Full text Link to item Cite

Werner syndrome protein interacts functionally with translesion DNA polymerases.

Journal Article Proc Natl Acad Sci U S A · June 19, 2007 Werner syndrome (WS) is characterized by premature onset of age-associated disorders and predisposition to cancer. The WS protein, WRN, encodes 3' --> 5' DNA helicase and 3' --> 5' DNA exonuclease activities, and is implicated in the maintenance of genomic ... Full text Link to item Cite

A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses.

Journal Article EMBO J · April 18, 2007 DNA damage causes genome instability and cell death, but many of the cellular responses to DNA damage still remain elusive. We here report a human protein, PALF (PNK and APTX-like FHA protein), with an FHA (forkhead-associated) domain and novel zinc-finger ... Full text Link to item Cite

RAD18 and poly(ADP-ribose) polymerase independently suppress the access of nonhomologous end joining to double-strand breaks and facilitate homologous recombination-mediated repair.

Journal Article Mol Cell Biol · April 2007 The Saccharomyces cerevisiae RAD18 gene is essential for postreplication repair but is not required for homologous recombination (HR), which is the major double-strand break (DSB) repair pathway in yeast. Accordingly, yeast rad18 mutants are tolerant of ca ... Full text Link to item Cite

DNA single-strand break repair is impaired in aprataxin-related ataxia.

Journal Article Ann Neurol · February 2007 OBJECTIVE: Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive form of cerebellar ataxia. The causative protein for EAOH/AOA1, aprataxin (APTX), interacts with X-ray ... Full text Link to item Cite

Replication-dependent and -independent responses of RAD18 to DNA damage in human cells.

Journal Article J Biol Chem · November 10, 2006 Postreplication repair facilitates tolerance of DNA damage during replication, overcoming termination of replication at sites of DNA damage. A major post-replication repair pathway in mammalian cells is translesion synthesis, which is carried out by specia ... Full text Link to item Cite

Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damage.

Journal Article Mol Cell · October 6, 2006 Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLQ is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) p ... Full text Link to item Cite

BLM is an early responder to DNA double-strand breaks.

Journal Article Biochem Biophys Res Commun · September 15, 2006 Bloom syndrome (BS) is an autosomal recessive disorder characterized by a marked predisposition to cancer and elevated genomic instability. The defective protein in BS, BLM, is a member of the RecQ helicase family and is believed to function in various DNA ... Full text Link to item Cite

Accumulation of Werner protein at DNA double-strand breaks in human cells.

Journal Article J Cell Sci · September 15, 2005 Werner syndrome is an autosomal recessive accelerated-aging disorder caused by a defect in the WRN gene, which encodes a member of the RecQ family of DNA helicases with an exonuclease activity. In vitro experiments have suggested that WRN functions in seve ... Full text Link to item Cite

DNA polymerase lambda protects mouse fibroblasts against oxidative DNA damage and is recruited to sites of DNA damage/repair.

Journal Article J Biol Chem · September 9, 2005 DNA polymerase lambda (pol lambda) is a member of the X family of DNA polymerases that has been implicated in both base excision repair and non-homologous end joining through in vitro studies. However, to date, no phenotype has been associated with cells d ... Full text Link to item Cite

MSH2-MSH6 stimulates DNA polymerase eta, suggesting a role for A:T mutations in antibody genes.

Journal Article J Exp Med · February 21, 2005 Activation-induced cytidine deaminase deaminates cytosine to uracil (dU) in DNA, which leads to mutations at C:G basepairs in immunoglobulin genes during somatic hypermutation. The mechanism that generates mutations at A:T basepairs, however, remains uncle ... Full text Link to item Cite

Translocation of XRCC1 and DNA ligase IIIalpha from centrosomes to chromosomes in response to DNA damage in mitotic human cells.

Journal Article Nucleic Acids Res · 2005 DNA single-strand breaks (SSBs) are the most frequent lesions caused by oxidative DNA damage. They disrupt DNA replication, give rise to double-strand breaks and lead to cell death and genomic instability. It has been shown that the XRCC1 protein plays a k ... Full text Link to item Cite

UV light-induced DNA damage and tolerance for the survival of nucleotide excision repair-deficient human cells.

Journal Article J Biol Chem · November 5, 2004 DNA damage can cause cell death unless it is either repaired or tolerated. The precise contributions of repair and tolerance mechanisms to cell survival have not been previously evaluated. Here we have analyzed the cell killing effect of the two major UV l ... Full text Link to item Cite

In situ analysis of repair processes for oxidative DNA damage in mammalian cells.

Journal Article Proc Natl Acad Sci U S A · September 21, 2004 Oxidative DNA damage causes blocks and errors in transcription and replication, leading to cell death and genomic instability. Although repair mechanisms of the damage have been extensively analyzed in vitro, the actual in vivo repair processes remain larg ... Full text Link to item Cite

Functional and physical interactions between ERCC1 and MSH2 complexes for resistance to cis-diamminedichloroplatinum(II) in mammalian cells.

Journal Article DNA Repair (Amst) · February 3, 2004 Bulky DNA lesions are mainly repaired by nucleotide excision repair (NER), in which the interaction of ERCC1 with XPA protein recruits the ERCC1-XPF complex, which acts as a structure-specific endonuclease in the repair process. However, additional functio ... Full text Link to item Cite

Spatial and temporal cellular responses to single-strand breaks in human cells.

Journal Article Mol Cell Biol · June 2003 DNA single-strand breaks (SSB) are one of the most frequent DNA lesions produced by reactive oxygen species and during DNA metabolism, but the analysis of cellular responses to SSB remains difficult due to the lack of an experimental method to produce SSB ... Full text Link to item Cite