P53 pathways involving G2 checkpoint regulators and the role of their subcellular localisation.

Abstract

DNA damage activates checkpoint pathways to produce a G1 or G2 cell cycle arrest and DNA repair. G2 checkpoint integrity prevents inappropriate mitosis of unrepaired DNA. Cell cycle progression is determined by cyclin-dependent kinase (CDK) enzymes in association with specific cyclin proteins, with Cdc2/cyclin B regulating mitosis. The tumour suppressor p53 re-enforces G2 arrest through the CDK inhibitor, p21(WAF1/CIPI). Functional regulation of G2 checkpoint proteins occurs through levels of protein expression, phosphorylation and subcellular localisation