Biochemistry Publications

Title

A G1 Checkpoint Mediated by the Retinoblastoma Protein That Is Dispensable in Terminal Differentiation but Essential for Senescence

Document Type

Article

Publication Date

2-2010

Journal

Molecular and Cellular Biology

Volume

30

Issue

4

First Page

948

Last Page

960

URL with Digital Object Identifier

http://dx.doi.org/10.1128/MCB.01168-09

Abstract

Terminally differentiated cell types are needed to live and function in a postmitotic state for a lifetime. Cellular senescence is another type of permanent arrest that blocks the proliferation of cells in response to genotoxic stress. Here we show that the retinoblastoma protein (pRB) uses a mechanism to block DNA replication in senescence that is distinct from its role in permanent cell cycle exit associated with terminal differentiation. Our work demonstrates that a subtle mutation in pRB that cripples its ability to interact with chromatin regulators impairs heterochromatinization and repression of E2F-responsive promoters during senescence. In contrast, terminally differentiated nerve and muscle cells bearing the same mutation fully exit the cell cycle and block E2F-responsive gene expression by a different mechanism. Remarkably, this reveals that pRB recruits chromatin regulators primarily to engage a stress-responsive G(1) arrest program.