Mus81-Mms4 functions as a single heterodimer to cleave nicked intermediates in recombinational DNA repair.

Détails

ID Serval
serval:BIB_711778FF9705
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mus81-Mms4 functions as a single heterodimer to cleave nicked intermediates in recombinational DNA repair.
Périodique
Molecular and cellular biology
Auteur⸱e⸱s
Schwartz E.K., Wright W.D., Ehmsen K.T., Evans J.E., Stahlberg H., Heyer W.D.
ISSN
1098-5549 (Electronic)
ISSN-L
0270-7306
Statut éditorial
Publié
Date de publication
08/2012
Peer-reviewed
Oui
Volume
32
Numéro
15
Pages
3065-3080
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The formation of crossovers is a fundamental genetic process. The XPF-family endonuclease Mus81-Mms4 (Eme1) contributes significantly to crossing over in eukaryotes. A key question is whether Mus81-Mms4 can process Holliday junctions that contain four uninterrupted strands. Holliday junction cleavage requires the coordination of two active sites, necessitating the assembly of two Mus81-Mms4 heterodimers. Contrary to this expectation, we show that Saccharomyces cerevisiae Mus81-Mms4 exists as a single heterodimer both in solution and when bound to DNA substrates in vitro. Consistently, immunoprecipitation experiments demonstrate that Mus81-Mms4 does not multimerize in vivo. Moreover, chromatin-bound Mus81-Mms4 does not detectably form higher-order multimers. We show that Cdc5 kinase activates Mus81-Mms4 nuclease activity on 3' flaps and Holliday junctions in vitro but that activation does not induce a preference for Holliday junctions and does not induce multimerization of the Mus81-Mms4 heterodimer. These data support a model in which Mus81-Mms4 cleaves nicked recombination intermediates such as displacement loops (D-loops), nicked Holliday junctions, or 3' flaps but not intact Holliday junctions with four uninterrupted strands. We infer that Mus81-dependent crossing over occurs in a noncanonical manner that does not involve the coordinated cleavage of classic Holliday junctions.
Mots-clé
Cell Cycle Proteins/metabolism, Chromatin/metabolism, DNA/genetics, DNA/metabolism, DNA, Cruciform/genetics, DNA, Cruciform/metabolism, DNA-Binding Proteins/metabolism, Endonucleases/metabolism, Flap Endonucleases/metabolism, Protein Multimerization, Protein Serine-Threonine Kinases/metabolism, Recombination, Genetic, Recombinational DNA Repair, Saccharomyces cerevisiae/genetics, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/06/2023 16:03
Dernière modification de la notice
28/07/2023 6:59
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