The influence of the proliferating cell nuclear antigen-interacting domain of p21(CIP1) on DNA synthesis catalyzed by the human and Saccharomyces cerevisiae polymerase δ holoenzymes Journal Article

  


Authors: Gibbs, E.; Kelman, Z.; Gulbis, J. M.; O'Donnell, M.; Kuriyan, J.; Burgers, P. M. J.; Hurwitz, J.
Article Title: The influence of the proliferating cell nuclear antigen-interacting domain of p21(CIP1) on DNA synthesis catalyzed by the human and Saccharomyces cerevisiae polymerase δ holoenzymes
Abstract: In eukaryotes, processive DNA synthesis catalyzed by DNA polymerases δ and ε (pol δ and ε) 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 p21(CIP1) due to a specific interaction between hPCNA and the carboxyl terminus of p21(CIP1). In this report, we show that Saccharomyces cerevisiae (S. cerevisiae) PCNA-dependent pol δ-catalyzed DNA synthesis was inhibited less efficiently than the human system by the intact p21(CIP1) protein and was unaffected by the p21(CIP1) carboxyl-terminal peptide (codons 139-160). This species-specific response of PCNA to p21(CIP1)-mediated inhibition of DNA synthesis results from a marked difference in the ability of h and S. cerevisiae PCNA to interact with p21(CIP1). As shown by binding studies using the surface plasmon resonance technique, hPCNA binds both full- length p21(CIP1) and the p21(CIP1) peptide-(139-160) stoichiometrically with a similar affinity (K(D) ~ 2.5 nM) while S. cerevisiae PCNA binds p21(CIP1) with ~10-fold less affinity and does not interact with the p21(CIP1) peptide-(139-160).
Keywords: nonhuman; binding affinity; dna replication; dna synthesis; dna repair; enzyme activity; species specificity; kinetics; saccharomyces cerevisiae; models, molecular; cyclin-dependent kinase inhibitor p21; catalysis; cycline; cyclins; fungal protein; proliferating cell nuclear antigen; dna-directed dna polymerase; dna directed dna polymerase delta; peptide analysis; fungal genetics; dna polymerase iii; dna, circular; humans; priority journal; article
Journal Title: Journal of Biological Chemistry
Volume: 272
Issue: 4
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 1997-01-24
Start Page: 2373
End Page: 2381
Language: English
DOI: 10.1074/jbc.272.4.2373
PUBMED: 8999948
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031018324&doi=10.1074%2fjbc.272.4.2373&partnerID=40&md5=ba24b5edda63df05cc8423056866fc8b
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
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MSK Authors
  1. Jerard Hurwitz
    206 Hurwitz
  2. Emma Gibbs
    14 Gibbs
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