ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage.

ABSTRACT: The mismatch repair pathway (MMR) is essential for removing DNA polymerase errors, thereby maintaining genomic stability. Loss of MMR function increases mutation frequency and is associated with tumorigenesis. However, how MMR is executed at active DNA replication forks is unclear. This has important implications for understanding how MMR repairs O⁶-methylguanine/thymidine (^MeG/T) mismatches created upon exposure to DNA alkylating agents. If ^MeG/T lesion recognition by MMR initiates mismatch excision, the reinsertion of a mismatched thymidine during resynthesis could initiate futile repair cycles. One consequence of futile repair cycles might be a disruption of overall DNA replication in the affected cell. Herein, we show that in MMR-proficient HeLa

SUBMITTER: Gupta D 

PROVIDER: S-EPMC5816205 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature