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Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks.

Publication ,  Journal Article
Zhao, J; Jain, A; Iyer, RR; Modrich, PL; Vasquez, KM
Published in: Nucleic Acids Res
July 2009

DNA interstrand crosslinks (ICLs) are among the most cytotoxic types of DNA damage, thus ICL-inducing agents such as psoralen, are clinically useful chemotherapeutics. Psoralen-modified triplex-forming oligonucleotides (TFOs) have been used to target ICLs to specific genomic sites to increase the selectivity of these agents. However, how TFO-directed psoralen ICLs (Tdp-ICLs) are recognized and processed in human cells is unclear. Previously, we reported that two essential nucleotide excision repair (NER) protein complexes, XPA-RPA and XPC-RAD23B, recognized ICLs in vitro, and that cells deficient in the DNA mismatch repair (MMR) complex MutSbeta were sensitive to psoralen ICLs. To further investigate the role of MutSbeta in ICL repair and the potential interaction between proteins from the MMR and NER pathways on these lesions, we performed electrophoretic mobility-shift assays and chromatin immunoprecipitation analysis of MutSbeta and NER proteins with Tdp-ICLs. We found that MutSbeta bound to Tdp-ICLs with high affinity and specificity in vitro and in vivo, and that MutSbeta interacted with XPA-RPA or XPC-RAD23B in recognizing Tdp-ICLs. These data suggest that proteins from the MMR and NER pathways interact in the recognition of ICLs, and provide a mechanistic link by which proteins from multiple repair pathways contribute to ICL repair.

Duke Scholars

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

July 2009

Volume

37

Issue

13

Start / End Page

4420 / 4429

Location

England

Related Subject Headings

  • Xeroderma Pigmentosum Group A Protein
  • Replication Protein A
  • MutS Homolog 3 Protein
  • MutS Homolog 2 Protein
  • Humans
  • Furocoumarins
  • Developmental Biology
  • DNA-Binding Proteins
  • DNA Repair Enzymes
  • DNA Mismatch Repair
 

Citation

APA
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ICMJE
MLA
NLM
Zhao, J., Jain, A., Iyer, R. R., Modrich, P. L., & Vasquez, K. M. (2009). Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks. Nucleic Acids Res, 37(13), 4420–4429. https://doi.org/10.1093/nar/gkp399
Zhao, Junhua, Aklank Jain, Ravi R. Iyer, Paul L. Modrich, and Karen M. Vasquez. “Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks.Nucleic Acids Res 37, no. 13 (July 2009): 4420–29. https://doi.org/10.1093/nar/gkp399.
Zhao J, Jain A, Iyer RR, Modrich PL, Vasquez KM. Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks. Nucleic Acids Res. 2009 Jul;37(13):4420–9.
Zhao, Junhua, et al. “Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks.Nucleic Acids Res, vol. 37, no. 13, July 2009, pp. 4420–29. Pubmed, doi:10.1093/nar/gkp399.
Zhao J, Jain A, Iyer RR, Modrich PL, Vasquez KM. Mismatch repair and nucleotide excision repair proteins cooperate in the recognition of DNA interstrand crosslinks. Nucleic Acids Res. 2009 Jul;37(13):4420–4429.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

July 2009

Volume

37

Issue

13

Start / End Page

4420 / 4429

Location

England

Related Subject Headings

  • Xeroderma Pigmentosum Group A Protein
  • Replication Protein A
  • MutS Homolog 3 Protein
  • MutS Homolog 2 Protein
  • Humans
  • Furocoumarins
  • Developmental Biology
  • DNA-Binding Proteins
  • DNA Repair Enzymes
  • DNA Mismatch Repair