CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication

Genes

María Belén de la Vega¹  VanesaGottifredi¹  Sebastián Omar Siri¹  Nicolás Luis Calzetta¹  Sabrina Florencia Mansilla¹ 

[1] Cell Cycle and Genomic Stability laboratory. Fundación Instituto Leloir. IIBBA-CONICET. Av. Patricias Argentinas 435, 1405 Buenos Aires, Argentina;

关键词: p21CDKN1A;    CDK;    PCNA;    TLS;    S phase;    DNA replication;   

DOI  :  10.3390/genes11060593

来源: DOAJ

【 摘 要 】

p21^Waf/CIP1 is a small unstructured protein that binds and inactivates cyclin-dependent kinases (CDKs). To this end, p21 levels increase following the activation of the p53 tumor suppressor. CDK inhibition by p21 triggers cell-cycle arrest in the G1 and G2 phases of the cell cycle. In the absence of exogenous insults causing replication stress, only residual p21 levels are prevalent that are insufficient to inhibit CDKs. However, research from different laboratories has demonstrated that these residual p21 levels in the S phase control DNA replication speed and origin firing to preserve genomic stability. Such an S-phase function of p21 depends fully on its ability to displace partners from chromatin-bound proliferating cell nuclear antigen (PCNA). Vice versa, PCNA also regulates p21 by preventing its upregulation in the S phase, even in the context of robust p21 induction by irradiation. Such a tight regulation of p21 in the S phase unveils the potential that CDK-independent functions of p21 may have for the improvement of cancer treatments.

【 授权许可】

Unknown