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The Pif1 helicase is actively inhibited during meiotic recombination which restrains gene conversion tract length

Abstract : Meiotic recombination ensures proper chromosome segregation to form viable gametes and results in gene conversions events between homologs. Conversion tracts are shorter in meiosis than in mitotically dividing cells. This results at least in part from the binding of a complex, containing the Mer3 helicase and the MutL␤ heterodimer, to meiotic recombination intermediates. The molecular actors inhibited by this complex are elusive. The Pif1 DNA helicase is known to stimulate DNA polymerase delta (Pol ␦)mediated DNA synthesis from D-loops, allowing long synthesis required for break-induced replication. We show that Pif1 is also recruited genome wide to meiotic DNA double-strand break (DSB) sites. We further show that Pif1, through its interaction with PCNA, is required for the long gene conversions observed in the absence of MutL␤ recruitment to recombination sites. In vivo, Mer3 interacts with the PCNA clamp loader RFC, and in vitro, Mer3-MutL␤ ensemble inhibits Pif1-stimulated D-loop extension by Pol ␦ and RFC-PCNA. Mechanistically, our results suggest that Mer3-MutL␤ may compete with Pif1 for binding to RFC-PCNA. Taken together, our data show that Pif1's activity that promotes meiotic DNA repair synthesis is restrained by the Mer3-MutL␤ ensemble which in turn prevents long gene conversion tracts and possibly associated mutagenesis.
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https://hal.sorbonne-universite.fr/hal-03251565
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Submitted on : Monday, June 7, 2021 - 10:58:52 AM
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Dipti Vernekar, Giordano Reginato, Céline Adam, Lepakshi Ranjha, Florent Dingli, et al.. The Pif1 helicase is actively inhibited during meiotic recombination which restrains gene conversion tract length. Nucleic Acids Research, Oxford University Press, 2021, 49 (8), pp.4522 - 4533. ⟨10.1093/nar/gkab232⟩. ⟨hal-03251565⟩

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