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Protein phosphatase 2A controls ongoing DNA replication by binding to and regulating cell division cycle 45 (CDC45).


ABSTRACT: Genomic replication is a highly regulated process and represents both a potential benefit and liability to rapidly dividing cells; however, the precise post-translational mechanisms regulating genomic replication are incompletely understood. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that regulates a diverse array of cellular processes. Here, utilizing both a gain-of-function chemical biology approach and loss-of-function genetic approaches to modulate PP2A activity, we found that PP2A regulates DNA replication. We demonstrate that increased PP2A activity can interrupt ongoing DNA replication, resulting in a prolonged S phase. The impaired replication resulted in a collapse of replication forks, inducing dsDNA breaks, homologous recombination, and a PP2A-dependent repl

SUBMITTER: Perl AL 

PROVIDER: S-EPMC6851307 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature