Role of p21WAF1 in the cellular response to UV.
UV or g irradiation mediated DNA damage activates p53 and induces cell cycle arrest. Induction of cyclin dependent kinase inhibitor p21WAF1 by p53 after DNA damage plays an important role in cell cycle arrest after gamma irradiation. The p53 mediated cell cycle arrest has been postulated to allow cells to repair the DNA damage. Repair of UV damaged DNA occurs primarily by the nucleotide excision pathway (NER). It is known that p21WAF1 binds PCNA and inhibits PCNA function in DNA replication. PCNA is also required for repair by NER but there have been conflicting reports on whether p21WAF1 can inhibit PCNA function in NER. It has therefore been difficult to integrate the UV induced cell cycle arrest by p21 in the context of repair of UV damaged DNA. A recent study reported that p21WAF1 protein is degraded after low but not high doses of UV irradiation, that cell cycle arrest after UV is p21 independent, and that at low dose UV irradiation p21WAF1 degradation is essential for optimal DNA repair. These findings shed new light on the role of p21 in the cellular response to UV and clarify some outstanding issues concerning p21WAF1 function.
Fotedar
Rati
R
Institut de Biologie Structurale J.-P. Ebel, Grenoble, France. fotedar@ibs.fr
Bendjennat
Mourad
M
Fotedar
Arun
A
D000818:Animals; D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects; D000071877:Checkpoint Kinase 1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology / Q000528:radiation effects*; D004260:DNA Repair / Q000502:physiology; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000528:radiation effects; D025801:Ubiquitin / Q000378:metabolism; D014466:Ultraviolet Rays; D020687:cdc25 Phosphatases / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases