Inactivation of Rb and E2f8 synergizes to trigger stressed DNA replication during erythroid terminal differentiation.

ABSTRACT: Rb is critical for promoting cell cycle exit in cells undergoing terminal differentiation. Here we show that during erythroid terminal differentiation, Rb plays a previously unappreciated and unorthodox role in promoting DNA replication and cell cycle progression. Specifically, inactivation of Rb in erythroid cells led to stressed DNA replication, increased DNA damage, and impaired cell cycle progression, culminating in defective terminal differentiation and anemia. Importantly, all of these defects associated with Rb loss were exacerbated by the concomitant inactivation of E2f8. Gene expression profiling and chromatin immunoprecipitation (ChIP) revealed that Rb and E2F8 cosuppressed a large array of E2F target genes that are critical for DNA replication and cell cycle progression. Remarka

SUBMITTER: Ghazaryan S 

PROVIDER: S-EPMC4135565 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature