The P21 Protein and DNA Damage

Radiation-induced DNA lesions lead to the activation of complex damage response pathways in mammalian cells. In one of these pathways the p21 protein, a well-characterized cyclin dependent kinase inhibitor, is induced by TP53 after DNA damage leading to cell cycle arrest in G1-phase. Independently of its transactivation by TP53, the p21 protein forms nuclear accumulations at heavy ion-induced DNA lesions [Jakob et al., 2000]. As shown in this study, p21 foci also arise after exposure of cells to sparsely ionizing X-rays. In an attempt to elucidate the functional role of these p21 foci, their dependence on the proliferating cell nuclear antigen (PCNA) is demonstrated here. In particular, the requirement for a functional interaction between p21 and PCNA is revealed. In addition, the kinetics of the PCNA- and p21- accumulations at heavy ion-induced DNA lesions is shown to be very similar, and both proteins are part of the chromatin-bound protein fraction after DNA damage induction by X-rays. A possible involvement of p21 in the DNA double- and/or single-strand break repair pathways is discussed