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Zakharyevich, Kseniya; Ma, Yunmei; Tang, Shangming; Hwang, Patty Yi-Hwa; Boiteux, Serge; Hunter, Neil (2010)
Publisher: Elsevier BV
Journal: Molecular Cell
Languages: English
Types: Article
Subjects: Molecular Biology, Cell Biology, Article
The Rad2/XPG family nuclease, Exo1, functions in a variety of DNA repair pathways. During meiosis, Exo1 promotes crossing-over and thereby facilitates chromosome segregation at the first division. Meiotic recombination is initiated by programmed DNA double-strand-breaks (DSBs). Nucleolytic resection of DSBs generates long 3′-single-strand tails that undergo strand-exchange with a homologous chromosome to form Joint Molecule (JM) intermediates. We show that meiotic DSB-resection is dramatically reduced in exo1Δ mutants and test the idea that Exo1-catalyzed resection promotes crossing-over by facilitating formation of crossover-specific JMs called double-Holliday Junctions (dHJs). Contrary to this idea, dHJs form at wild-type levels in exo1Δ mutants implying that Exo1 has a second function that promotes resolution of dHJs into crossovers. Surprisingly, the dHJ resolution function of Exo1 is independent of its nuclease activities, but requires interaction with the putative endonuclease complex, Mlh1-Mlh3. Thus, the DSB-resection and pro-crossover functions of Exo1 during meiosis involve temporally and biochemically distinct activities.
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