气候变化领域集成服务门户(CCPortal): Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation

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DOI	10.1073/PNAS.2022704118
	Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation
	Dai J.; Sanchez A.; Adam C.; Ranjha L.; Reginato G.; Chervy P.; Tellier-Lebegue C.; Andreani J.; Guérois R.; Ropars V.; Le Du M.-H.; Maloisel L.; Martini E.; Legrand P.; Thureau A.; Cejka P.; Borde V.; Charbonniera J.-B.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:23
英文摘要	In budding yeast, the MutL homolog heterodimer Mlh1-Mlh3 (MutLγ) plays a central role in the formation of meiotic crossovers. It is also involved in the repair of a subset of mismatches besides the main mismatch repair (MMR) endonuclease Mlh1-Pms1 (MutLα). The heterodimer interface and endonuclease sites of MutLγ and MutLα are located in their C-terminal domain (CTD). The molecular basis of MutLγ's dual roles in MMR and meiosis is not known. To better understand the specificity of MutLγ, we characterized the crystal structure of Saccharomyces cerevisiae MutLγ(CTD). Although MutLγ(CTD) presents overall similarities with MutLα(CTD), it harbors some rearrangement of the surface surrounding the active site, which indicates altered substrate preference. The last amino acids of Mlh1 participate in the Mlh3 endonuclease site as previously reported for Pms1. We characterized mlh1 alleles and showed a critical role of this Mlh1 extreme C terminus both in MMR and in meiotic recombination. We showed that the MutLγ(CTD) preferentially binds Holliday junctions, contrary to MutLα(CTD). We characterized Mlh3 positions on the N-terminal domain (NTD) and CTD that could contribute to the positioning of the NTD close to the CTD in the context of the full-length MutLγ. Finally, crystal packing revealed an assembly of MutLγ(CTD) molecules in filament structures. Mutation at the corresponding interfaces reduced crossover formation, suggesting that these superstructures may contribute to the oligomer formation proposed for MutLγ. This study defines clear divergent features between theMutL homologs and identifies, at the molecular level, their specialization toward MMR or meiotic recombination functions. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Biochemistry; DNA recombination; DNA repair; Genetics; Structural biology
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238930
作者单位	Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, 91198, France; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3244, Dynamics of Genetic Information, Paris, 75248, France; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, 6500, Switzerland; Department of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), Zürich, 8093, Switzerland; Institute of Cellular and Molecular Radiobiology, Institut de Biologie François Jacob, CEA, Fontenay-aux-Roses, 92265, France; Universités Paris Diderot and Paris Sud, Fontenay-aux-Roses, F-92265, France; Synchrotron SOLEIL, L'Orme des Merisiers, BP 48 91192 Gif-sur-Yvette, Saint Aubin, France
推荐引用方式 GB/T 7714	Dai J.,Sanchez A.,Adam C.,et al. Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation[J],2021,118(23).
APA	Dai J..,Sanchez A..,Adam C..,Ranjha L..,Reginato G..,...&Charbonniera J.-B..(2021).Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation.Proceedings of the National Academy of Sciences of the United States of America,118(23).
MLA	Dai J.,et al."Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation".Proceedings of the National Academy of Sciences of the United States of America 118.23(2021).