Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection.

ABSTRACT: Rad6 and Bre1, ubiquitin-conjugating E2 and E3 enzymes respectively, are responsible for histone H2B lysine 123 mono-ubiquitination (H2Bub1) in Saccharomyces cerevisiae. Previous studies have shown that Rad6 and Bre1 regulate telomere length and recombination. However, the underlying molecular mechanism remains largely unknown. Here we report that H2BK123 mutation results in telomere shortening, while inactivation of Ubp8 and/or Ubp10, deubiquitinases of H2Bub1, leads to telomere lengthening in Rad6-Bre1-dependent manner. In telomerase-deficient cells, inactivation of Rad6-Bre1 pathway retards telomere shortening rate and the onset of senescence, while deletion of UBP8 and/or UBP10 accelerates senescence. Thus, Rad6-Bre1 pathway regulates both telomere length and recombination through its

SUBMITTER: Wu Z 

PROVIDER: S-EPMC5389628 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature