The DNA replication checkpoint targets the kinetochore to reposition DNA structure-induced replication damage to the nuclear periphery.

ABSTRACT: Hairpin-forming CAG/CTG repeats pose significant challenges to DNA replication. In S. cerevisiae, long CAG/CTG repeat tracts reposition from the interior of the nucleus to the nuclear pore complex (NPC) to maintain their integrity. We show that relocation of a (CAG/CTG)₁₃₀ tract to the NPC is dependent on phosphorylation of Mrc1 (hClaspin) of the fork protection complex and activation of the Mrc1/Rad53 replication checkpoint, implicating an uncoupled fork as the initial damage signal. Dun1-mediated phosphorylation of the kinetochore protein Cep3 is required for repositioning, a constraint that can be overcome by centromere inactivation, connecting detachment of the kinetochore from microtubule ends to NPC association. Activation of this pathway leads to the formation of DNA dama

SUBMITTER: Maclay TM 

PROVIDER: S-EPMC12435773 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature