4.5 Article

ATP-dependent chromatin remodeling shapes the DNA replication landscape

Journal

NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 15, Issue 5, Pages 477-484

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1419

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Funding

  1. NCI NIH HHS [T32 CA009657] Funding Source: Medline
  2. NIGMS NIH HHS [R01 GM058465, R01 GM058465-10A1] Funding Source: Medline

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The eukaryotic DNA replication machinery must traverse every nucleosome in the genome during S phase. As nucleosomes are generally inhibitory to DNA-dependent processes, chromatin structure must undergo extensive reorganization to facilitate DNA synthesis. However, the identity of chromatin-remodeling factors involved in replication and how they affect DNA synthesis is largely unknown. Here we show that two highly conserved ATP-dependent chromatin-remodeling complexes in Saccharomyces cerevisiae, Isw2 and Ino80, function in parallel to promote replication fork progression. As a result, Isw2 and Ino80 have especially important roles for replication of late-replicating regions during periods of replication stress. Both Isw2 and Ino80 complexes are enriched at sites of replication, suggesting that these complexes act directly to promote fork progression. These findings identify ATP-dependent chromatin-remodeling complexes that promote DNA replication and define a specific stage of replication that requires remodeling for normal function.

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