A Surveillance Mechanism Ensures Repair of DNA Lesions during Zygotic Reprogramming.

ABSTRACT: Sexual reproduction culminates in a totipotent zygote with the potential to produce a whole organism. Sperm chromatin reorganization and epigenetic reprogramming that alter DNA and histone modifications generate a totipotent embryo. Active DNA demethylation of the paternal genome has been proposed to involve base excision and DNA repair-based mechanisms. The nature and consequence of DNA lesions generated during reprogramming are not known. Using mouse genetics and chemical biology, we discovered that Tet3-dependent zygotic reprogramming generates paternal DNA lesions that are monitored by a surveillance mechanism. In vivo structure-function rescue assays revealed that cohesin-dependent repair of paternal DNA lesions prevents activation of a Chk1-dependent checkpoint that delays mitotic en

SUBMITTER: Ladstatter S 

PROVIDER: S-EPMC5161750 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature