Rad51–Rad52 Mediated Maintenance of Centromeric Chromatin in

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The epigenetic mark of centromeres, CENP-A, is deposited in S phase in most yeasts by a mechanism that is not completely understood. Here, we identify two CEN7 flanking replication origins, ORI7-L1 and ORI7-RI, proximal to an early replicating centromere (CEN7) in a budding yeast Candida albicans. Replication forks starting from these origins stall randomly at CEN7 by the kinetochore that serves as a barrier to fork progression. We observe that centromeric fork stalling is reduced in absence of the HR proteins, Rad51 and Rad52, known to play a role in restarting stalled forks. Further, we demonstrate that Rad51 and Rad52 physically interact with CENP-ACaCse4 in vivo. CENP-ACaCse4 levels are reduced in absence of Rad51 or Rad52, which results in disruption of the kinetochore structure. Here we propose a novel DNA replication-coupled mechanism mediated by HR proteins which epigenetically maintains centromere identity by regulating CENP-A deposition. A direct role of DNA repair proteins in centromere function offers insights into the mechanisms of centromere mis-regulation that leads to widespread aneuploidy in cancer cells.

Vyšlo v časopise: Rad51–Rad52 Mediated Maintenance of Centromeric Chromatin in. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004344
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004344

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