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J Biol Chem. 2009 Dec 18;284(51):35325-37. doi: 10.1074/jbc.M109.035949.

Cyclin E is stabilized in response to replication fork barriers leading to prolonged S phase arrest.

Author information

1
Department of Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract

Cyclin E is a regulator of cyclin-dependent protein kinases (Cdks) and is involved in mediating the cell cycle transition from G(1) to S phase. Here, we describe a novel function for cyclin E in the long term maintenance of checkpoint arrest in response to replication barriers. Exposure of cells to mitomycin C or UV irradiation, but not ionizing radiation, induces stabilization of cyclin E. Stabilization of cyclin E reduces the activity of Cdk2-cyclin A, resulting in a slowing of S phase progression and arrest. In addition, cyclin E is shown to be required for stabilization of Cdc6, which is required for activation of Chk1 and the replication checkpoint pathway. Furthermore, the stabilization of cyclin E in response to replication fork barriers depends on ATR, but not Nbs1 or Chk1. These results indicate that in addition to its well studied role in promoting cell cycle progression, cyclin E also has a role in regulating cell cycle arrest in response to DNA damage.

PMID:
19812034
PMCID:
PMC2790962
DOI:
10.1074/jbc.M109.035949
[Indexed for MEDLINE]
Free PMC Article

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