Pathways governing G1/S transition and their response to DNA damage

FEBS Letters

Lukas, Jiri¹  Bartek, Jiri¹ 

[1] Department of Cell Cycle and Cancer, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark

关键词: G1/S control;    Retinoblastoma protein;    E2F;    Myc;    Cyclin E–cyclin-dependent kinase 2;    Cdc25A;    p53;    DNA damage;    pRB;    retinoblastoma protein;    Cdk;    cyclin-dependent kinase;    ATM;    ataxia telangiectasia mutated;    ATR;    ataxia telangiectasia related;   

DOI  :  10.1016/S0014-5793(01)02114-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The ability to self-replicate is a fundamental feature of life, reflected at the cellular level by a highly regulated process initiated in G1 phase via commitment to a round of DNA replication and cell division. Here we briefly highlight recent advances in understanding the molecular pathways which govern the decision of mammalian somatic cells to enter S phase, and the so-called cell cycle checkpoints which guard the G1/S transition and S phase progression against potentially deleterious effects of genotoxic stress. Particular emphasis is put on the emerging parallel yet cooperative pathways of retinoblastoma protein (pRB)–E2F and Myc, their convergence to control the activity of the cyclin-dependent kinase 2 (Cdk2) at the G1/S boundary, as well as the two waves of checkpoint responses at G1/S: the rapid pathway(s) leading to Cdc25A degradation, and the delayed p53–p21 cascade, both silencing the Cdk2 activity upon DNA damage.

【 授权许可】

Unknown