Yeast Mphl helicase dissociates Rad51-made D-loops: Implications for crossover control in mitotic recombination

Rohit Prakash, Dominik Satory, Eloïse Dray, Almas Papusha, Jürgen Scheller, Wilfried Kramer, Lumir Krejci, Hannah Klein, James E. Haber, Patrick Sung, Grzegorz Ira

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

Eukaryotes possess mechanisms to limit crossing over during mitotic homologous recombination, thus avoiding possible chromosomal rearrangements. We show here that budding yeast Mph1, an ortholog of human FancM helicase, utilizes its helicase activity to suppress spontaneous unequal sister chromatid exchanges and DNA double-strand break-induced chromosome crossovers. Since the efficiency and kinetics of break repair are unaffected, Mph1 appears to channel repair intermediates into a noncrossover pathway. Importantly, Mph1 works independently of two other helicases - Srs2 and Sgs1 - that also attenuate crossing over. By chromatin immunoprecipitation, we find targeting of Mph1 to double-strand breaks in cells. Purified Mph1 binds D-loop structures and is particularly adept at unwinding these structures. Importantly, Mph1, but not a helicase-defective variant, dissociates Rad51-made D-loops. Overall, the results from our analyses suggest a new role of Mph1 in promoting the noncrossover repair of DNA double-strand breaks.

Original languageEnglish (US)
Pages (from-to)67-79
Number of pages13
JournalGenes and Development
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Crossing over
  • Dna helicase
  • Fanconi anemia
  • Genome instability
  • Recombination

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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