Regulates the Activity of PCNA

The cyclin-dependent kinase (CDK) inhibitor p21 (also known as p2l ) plays an important role in several cellular pathways in response to intracellular and extracellular stimuli. In particular, p53-dependent induction of p21 after DNA damage leads to inhibition of cell cycle progression and DNA replication. In addition, p21 is clearly involved in other processes like senescence, differentiation, and r ulation of gene expression.  

Recent work by our group has shown that in vitro p21 is also able to compete with PARP-1 and displace it from the interdomain connector loop of PCNA In vivo, after MNNG-induced DNA damage, p21 interacts with PARP-1, but not with chromatin-bound PCNA, i.e., the form involved in DNA repair. These results surest that PARP-1 may sequester p21, probably to avoid an untimely interaction with PCNA, which would Inhibit DNA repair. 

The r ion of the interdomain connector loop of PCNA that is involved in the association with pol 5 is identical to the sequence interacting with the C-terminus of p21 Competi- 

We acknowledge Drs. I. Frouin, G. Maga, M. Denari and F. Riva (IGM-CNI for their contribution to the experimental work presented here. Research was supported by the Italian C NR and MIUR (FIRB Projea RBNE0132MY). 

Poly (ADP-ribose) polymerase inhibits DNA replication by human replicative DNA polymerase a, P and e in vitro. FEES Lett 1994 356 261-266. 

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