Leading and lagging strand abasic sites differentially affect vertebrate replisome progression but involve analogous bypass mechanisms.

ABSTRACT: Abasic sites are frequent DNA lesions that interfere with replication and exert complex biological effects because they can be processed into other lesions. Thus, it remains poorly understood how abasic sites affect replisome progression, which repair pathways they elicit, and whether this depends on the template strand damaged. Using Xenopus egg extracts, we developed an approach to analyze replication of DNA containing a site-specific, stable abasic site on the leading or lagging strand template. We show that abasic sites robustly stall DNA synthesis but exert strand-specific effects. Leading strand abasic sites stall leading strands at the lesion, while lagging strands stall downstream at template-dependent positions. We conclude that replisomes uncouple at leading strand lesions, then

SUBMITTER: Cranford MT 

PROVIDER: S-EPMC12481018 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature