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David MacAlpine

Professor of Pharmacology and Cancer Biology
Pharmacology & Cancer Biology
Duke Box 3813, Durham, NC 27710
LSRC C333, Durham, NC 27710

Featured Works


Chromatin signatures of the Drosophila replication program.

Journal article Genome Res · February 2011 Featured Publication DNA replication initiates from thousands of start sites throughout the Drosophila genome and must be coordinated with other ongoing nuclear processes such as transcription to ensure genetic and epigenetic inheritance. Considerable progress has been made to ... Full text Link to item Cite

Identification of functional elements and regulatory circuits by Drosophila modENCODE.

Journal article Science · December 24, 2010 Featured Publication To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal p ... Full text Link to item Cite

Preferential re-replication of Drosophila heterochromatin in the absence of geminin.

Journal article PLoS Genet · September 9, 2010 Featured Publication To ensure genomic integrity, the genome must be duplicated exactly once per cell cycle. Disruption of replication licensing mechanisms may lead to re-replication and genomic instability. Cdt1, also known as Double-parked (Dup) in Drosophila, is a key regul ... Full text Link to item Cite

Conserved nucleosome positioning defines replication origins.

Journal article Genes Dev · April 15, 2010 Featured Publication The origin recognition complex (ORC) specifies replication origin location. The Saccharomyces cerevisiae ORC recognizes the ARS (autonomously replicating sequence) consensus sequence (ACS), but only a subset of potential genomic sites are bound, suggesting ... Full text Link to item Cite

Expression in aneuploid Drosophila S2 cells.

Journal article PLoS Biol · February 23, 2010 Featured Publication Extensive departures from balanced gene dose in aneuploids are highly deleterious. However, we know very little about the relationship between gene copy number and expression in aneuploid cells. We determined copy number and transcript abundance (expressio ... Full text Open Access Link to item Cite

Drosophila ORC localizes to open chromatin and marks sites of cohesin complex loading.

Journal article Genome Res · February 2010 Featured Publication The origin recognition complex (ORC) is an essential DNA replication initiation factor conserved in all eukaryotes. In Saccharomyces cerevisiae, ORC binds to specific DNA elements; however, in higher eukaryotes, ORC exhibits little sequence specificity in ... Full text Link to item Cite

Unlocking the secrets of the genome.

Journal article Nature · June 18, 2009 Featured Publication UNLABELLED: Despite the successes of genomics, little is known about how genetic information produces complex organisms. A look at the crucial functional elements of fly and worm genomes could change that. SUPPLEMENTARY INFORMATION: The online version of t ... Full text Link to item Cite

Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells.

Journal article Genes Dev · November 15, 2007 Featured Publication Myb-MuvB (MMB)/dREAM is a nine-subunit complex first described in Drosophila as a repressor of transcription, dependent on E2F2 and the RBFs. Myb, an integral member of MMB, curiously plays no role in the silencing of the test genes previously analyzed. Mo ... Full text Link to item Cite

Drosophila follicle cell amplicons as models for metazoan DNA replication: a cyclinE mutant exhibits increased replication fork elongation.

Journal article Proc Natl Acad Sci U S A · October 23, 2007 Featured Publication Gene clusters amplified in the ovarian follicle cells of Drosophila serve as powerful models for metazoan DNA replication. In response to developmental signals, specific genomic regions undergo amplification by repeated firing of replication origins and bi ... Full text Link to item Cite

Genome-wide analysis of re-replication reveals inhibitory controls that target multiple stages of replication initiation.

Journal article Mol Biol Cell · May 2006 Featured Publication DNA replication must be tightly controlled during each cell cycle to prevent unscheduled replication and ensure proper genome maintenance. The currently known controls that prevent re-replication act redundantly to inhibit pre-replicative complex (pre-RC) ... Full text Link to item Cite

Temporal profile of replication of human chromosomes.

Journal article Proc Natl Acad Sci U S A · May 3, 2005 Featured Publication Chromosomes in human cancer cells are expected to initiate replication from predictably localized origins, firing reproducibly at discrete times in S phase. Replication products obtained from HeLa cells at different stages of S phase were hybridized to cDN ... Full text Link to item Cite

A genomic view of eukaryotic DNA replication.

Journal article Chromosome Res · 2005 Featured Publication Recent advances in DNA microarray technology have enabled eukaryotic replication to be studied at whole-chromosome and genome-wide levels. These studies have provided new insights into the mechanisms that influence origin selection and the temporally co-or ... Full text Link to item Cite

Coordination of replication and transcription along a Drosophila chromosome.

Journal article Genes Dev · December 15, 2004 Featured Publication The mechanisms by which metazoan origins of DNA replication are defined, regulated, and influenced by chromosomal events remain poorly understood. To gain insights into these mechanisms, we developed a systematic approach using a Drosophila high-resolution ... Full text Link to item Cite

The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote.

Journal article Genes Dev · June 1, 2004 Featured Publication The covalent modification of nucleosomal histones has emerged as a major determinant of chromatin structure and gene activity. To understand the interplay between various histone modifications, including acetylation and methylation, we performed a genome-w ... Full text Link to item Cite

Visualization of replication initiation and elongation in Drosophila.

Journal article J Cell Biol · October 28, 2002 Featured Publication Chorion gene amplification in the ovaries of Drosophila melanogaster is a powerful system for the study of metazoan DNA replication in vivo. Using a combination of high-resolution confocal and deconvolution microscopy and quantitative realtime PCR, we foun ... Full text Link to item Cite