The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease.

Autor:	Pannafino G; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA., Chen JJ; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA., Mithani V; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA., Payero L; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA., Gioia M; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA., Crickard JB; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA., Alani E; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Jazyk:	angličtina
Zdroj:	Genetics [Genetics] 2024 Jul 08; Vol. 227 (3).
DOI:	10.1093/genetics/iyae066
Abstrakt:	The accurate segregation of homologous chromosomes during the Meiosis I reductional division in most sexually reproducing eukaryotes requires crossing over between homologs. In baker's yeast approximately 80% of meiotic crossovers result from Mlh1-Mlh3 and Exo1 acting to resolve double-Holliday junction intermediates in a biased manner. Little is known about how Mlh1-Mlh3 is recruited to recombination intermediates to perform its role in crossover resolution. We performed a gene dosage screen in baker's yeast to identify novel genetic interactors with Mlh1-Mlh3. Specifically, we looked for genes whose lowered dosage reduced meiotic crossing over using sensitized mlh3 alleles that disrupt the stability of the Mlh1-Mlh3 complex and confer defects in mismatch repair but do not disrupt meiotic crossing over. To our surprise we identified genetic interactions between MLH3 and DMC1, the recombinase responsible for recombination between homologous chromosomes during meiosis. We then showed that Mlh3 physically interacts with Dmc1 in vitro and in vivo. Partial complementation of Mlh3 crossover functions was observed when MLH3 was expressed under the control of the CLB1 promoter (NDT80 regulon), suggesting that Mlh3 function can be provided late in meiotic prophase at some functional cost. A model for how Dmc1 could facilitate Mlh1-Mlh3's role in crossover resolution is presented. Competing Interests: Conflicts of interest The author declare no conflicts of interest. (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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