title: Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions.
abstract: During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4(Eme1). Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastrophe.
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Alice
authors.initials: A
authors.lastname: Copsey
authors.affiliation: Howard Hughes Medical Institute, University of California, Davis, Davis, California, United States of America ; Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, California, United States of America.
authors.forename: Shangming
authors.initials: S
authors.lastname: Tang
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Jordan
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
authors.forename: Hannah G
authors.initials: HG
authors.lastname: Blitzblau
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Sonya
authors.initials: S
authors.lastname: Newcombe
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Andrew Chi-Ho
authors.initials: AC
authors.lastname: Chan
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Newnham
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Zhaobo
authors.initials: Z
authors.lastname: Li
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gray
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Alex D
authors.initials: AD
authors.lastname: Herbert
authors.affiliation: Department of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Prakash
authors.initials: P
authors.lastname: Arumugam
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America ; Department of Biology, New York University, New York, New York, United States of America.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochwagen
authors.affiliation: Howard Hughes Medical Institute, University of California, Davis, Davis, California, United States of America ; Department of Microbiology & Molecular Genetics, University of California, Davis, Davis, California, United States of America ; Department of Biology, New York University, New York, New York, United States of America ; Department of Molecular & Cellular Biology, University of California, Davis, Davis, California, United States of America ; Department of Cell Biology & Human Anatomy, University of California, Davis, Davis, California, United States of America.
authors.forename: Neil
authors.initials: N
authors.lastname: Hunter
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom.
authors.forename: Eva
authors.initials: E
authors.lastname: Hoffmann
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002503:Centromere; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination / Q000235:genetics*; D008540:Meiosis / Q000235:genetics*; D046912:Multiprotein Complexes / Q000235:genetics; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D000097722:Cohesins
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D004720:Endonucleases; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C486627:SMC5 protein, S cerevisiae; C108312:condensin complexes; C411624:MUS81 protein, S cerevisiae