MHF1–2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination

Sonali Bhattacharjee, Fekret Osman, Laura Feeney, Alexander Lorenz, Claire Bryer, Matthew C. Whitby

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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.
Original languageEnglish
Article number130102
Number of pages14
JournalOpen Biology
Volume13
Issue number9
DOIs
Publication statusPublished - 11 Sep 2013

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Keywords

  • anaphase bridge
  • centromere
  • DNA helicase
  • DNA replication
  • homologous recombination

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