The influence of the proliferating cell nuclear antigen-interacting domain of p21(CIP1) on DNA synthesis catalyzed by the human and Saccharomyces cerevisiae polymerase delta holoenzymes
1997
Gibbs, E. | Kelman, Z. | Gulbis, J.M. | O'Donnell, M. | Kuriyan, J. | Burgers, P.M.J. | Hurwitz, J.
In eukaryotes, processive DNA synthesis catalyzed by DNA polymerases delta and epsilon (pol delta and epsilon) requires the proliferating cell nuclear antigen (PCNA). It has recently been shown that in humans (h), the PCNA function, required for both DNA replication and nucleotide excision repair, can be inactivated by p21CIP1 due to a specific interaction between hPCNA and the carboxyl terminus of p21CIP1. In this report, we show that Saccharomyces cerevisiae (S. cerevisiae) PCNA-dependent pol delta-catalyzed DNA synthesis was inhibited less efficiently than the human system by the intact p21CIP1 protein and was unaffected by the p21CIP1 carboxyl-terminal peptide (codons 139-160). This species-specific response of PCNA to p21CIP1-mediated inhibition of DNA synthesis results from a marked difference in the ability of h and S. cerevisiae PCNA to interact with p21CIP1. As shown by binding studies using the surface plasmon resonance technique, hPCNA binds both full-length p21CIP1 and the p21CIP1 peptide-(139-160) stoichiometrically with a similar affinity (KD approximately 2.5 nM) while S. cerevisiae PCNA binds p21CIP1 with approximately 10-fold less affinity and does not interact with the p21CIP1 peptide-(139-160).
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