Recombination at DNA replication fork barriers is not universal and is differentially regulated by Swi1

Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4770-5. doi: 10.1073/pnas.0807739106. Epub 2009 Mar 9.

Abstract

DNA replication stress has been implicated in the etiology of genetic diseases, including cancers. It has been proposed that genomic sites that inhibit or slow DNA replication fork progression possess recombination hotspot activity and can form potential fragile sites. Here we used the fission yeast, Schizosaccharomyces pombe, to demonstrate that hotspot activity is not a universal feature of replication fork barriers (RFBs), and we propose that most sites within the genome that form RFBs do not have recombination hotspot activity under nonstressed conditions. We further demonstrate that Swi1, the TIMELESS homologue, differentially controls the recombination potential of RFBs, switching between being a suppressor and an activator of recombination in a site-specific fashion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • DNA Replication*
  • DNA-Binding Proteins / metabolism*
  • Models, Genetic
  • Recombination, Genetic / genetics*
  • Regulatory Sequences, Nucleic Acid / genetics
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Schizosaccharomyces pombe Proteins
  • swi1 protein, S pombe