RB-dependent S-phase response to DNA damage.

Abstract:

:The retinoblastoma tumor suppressor protein (RB) is a potent inhibitor of cell proliferation. RB is expressed throughout the cell cycle, but its antiproliferative activity is neutralized by phosphorylation during the G(1)/S transition. RB plays an essential role in the G(1) arrest induced by a variety of growth inhibitory signals. In this report, RB is shown to also be required for an intra-S-phase response to DNA damage. Treatment with cisplatin, etoposide, or mitomycin C inhibited S-phase progression in Rb(+/+) but not in Rb(-/-) mouse embryo fibroblasts. Dephosphorylation of RB in S-phase cells temporally preceded the inhibition of DNA synthesis. This S-phase dephosphorylation of RB and subsequent inhibition of DNA replication was observed in p21(Cip1)-deficient cells. The induction of the RB-dependent intra-S-phase arrest persisted for days and correlated with a protection against DNA damage-induced cell death. These results demonstrate that RB plays a protective role in response to genotoxic stress by inhibiting cell cycle progression in G(1) and in S phase.

journal_name

Mol Cell Biol

authors

Knudsen KE,Booth D,Naderi S,Sever-Chroneos Z,Fribourg AF,Hunton IC,Feramisco JR,Wang JY,Knudsen ES

doi

10.1128/mcb.20.20.7751-7763.2000

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

7751-63

issue

20

eissn

0270-7306

issn

1098-5549

journal_volume

20

pub_type

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