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Proliferating Cell Nuclear Antigen-dependent Coordination of the Biological Functions of Human DNA Polymerase ?
journal contributionposted 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.
JournalJournal of Biological Chemistry
PublisherAmerican Society for Biochemistry and Molecular Biology
Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
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