title: MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination.
abstract: The histone-fold proteins Mhf1/CENP-S and Mhf2/CENP-X perform two important functions in vertebrate cells. First, they are components of the constitutive centromere-associated network, aiding kinetochore assembly and function. Second, they work with the FANCM DNA translocase to promote DNA repair. However, it has been unclear whether there is crosstalk between these roles. We show that Mhf1 and Mhf2 in fission yeast, as in vertebrates, serve a dual function, aiding DNA repair/recombination and localizing to centromeres to promote chromosome segregation. Importantly, these functions are distinct, with the former being dependent on their interaction with the FANCM orthologue Fml1 and the latter not. Together with Fml1, they play a second role in aiding chromosome segregation by processing sister chromatid junctions. However, a failure of this activity does not manifest dramatically increased levels of chromosome missegregation due to the Mus81-Eme1 endonuclease, which acts as a failsafe to resolve DNA junctions before the end of mitosis.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Sonali
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Fekret
authors.initials: F
authors.lastname: Osman
authors.forename: Laura
authors.initials: L
authors.lastname: Feeney
authors.forename: Alexander
authors.initials: A
authors.lastname: Lorenz
authors.forename: Claire
authors.initials: C
authors.lastname: Bryer
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Whitby
mesh_terms: D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000378:metabolism*; D020090:Chromosome Segregation; D004265:DNA Helicases / Q000032:analysis / Q000378:metabolism*; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D008938:Mitosis; D060066:Protein Interaction Maps; D011995:Recombination, Genetic; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C495865:MUS81 protein, S pombe; C587034:Mhf2 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C442837:Eme1 protein, S pombe; D004720:Endonucleases; C573663:Fml1 protein, S pombe; D004265:DNA Helicases; C587033:Mhf1 protein, S pombe
keywords: DNA helicase; DNA replication; anaphase bridge; centromere; homologous recombination
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