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Proliferating Cell Nuclear Antigen-dependent Coordination of the Biological Functions of Human DNA Polymerase ?

journal contribution
posted on 2023-06-08, 07:03 authored by Antonio E Vidal, Patricia Kannouche, Vladimir N Podust, Wei Yang, Alan LehmannAlan Lehmann, Roger Woodgate
Y-family DNA polymerases are believed to facilitate the replicative bypass of damaged DNA in a process commonly referred to as translesion synthesis. With the exception of DNA polymerase ? (pol?), which is defective in humans with the Xeroderma pigmentosum variant (XP-V) phenotype, little is known about the cellular function(s) of the remaining human Y-family DNA polymerases. We report here that an interaction between human DNA polymerase ? (pol?) and the proliferating cell nuclear antigen (PCNA) stimulates the processivity of pol? in a template-dependent manner in vitro. Mutations in one of the putative PCNA-binding motifs (PIP box) of pol? or the interdomain connector loop of PCNA diminish the binding between pol? and PCNA and concomitantly reduce PCNA-dependent stimulation of pol? activity. Furthermore, although retaining its capacity to interact with pol? in vivo, the pol?-PIP box mutant fails to accumulate in replication foci. Thus, PCNA, acting as both a scaffold and a modulator of the different activities involved in replication, appears to recruit and coordinate replicative and translesion DNA synthesis polymerases to ensure genome integrity.

History

Publication status

  • Published

Journal

Journal of Biological Chemistry

ISSN

0021-9258

Publisher

American Society for Biochemistry and Molecular Biology

Issue

46

Volume

279

Page range

48360-48368

Pages

9.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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