ATP-dependent chromatin remodeling shapes the DNA replication landscape

Nat Struct Mol Biol. 2008 May;15(5):477-84. doi: 10.1038/nsmb.1419. Epub 2008 Apr 13.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism*
  • Chromatin Assembly and Disassembly*
  • DNA Replication*
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism
  • Methyl Methanesulfonate / pharmacology
  • Mutation
  • Nucleosomes / metabolism
  • S Phase
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • High Mobility Group Proteins
  • INO80 complex, S cerevisiae
  • ISWI protein
  • NHP10 protein, S cerevisiae
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Adenosine Triphosphate
  • Methyl Methanesulfonate
  • Adenosine Triphosphatases