Vidal, Antonio E, Kannouche, Patricia, Podust, Vladimir N, Yang, Wei, Lehmann, Alan R and Woodgate, Roger (2004) Proliferating Cell Nuclear Antigen-dependent Coordination of the Biological Functions of Human DNA Polymerase ι. Journal of Biological Chemistry, 279 (46). pp. 48360-48368. ISSN 0021-9258

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Abstract

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 η (polη), 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 ι (polι) and the proliferating cell nuclear antigen (PCNA) stimulates the processivity of polι in a template-dependent manner in vitro. Mutations in one of the putative PCNA-binding motifs (PIP box) of polι or the interdomain connector loop of PCNA diminish the binding between polι and PCNA and concomitantly reduce PCNA-dependent stimulation of polι activity. Furthermore, although retaining its capacity to interact with polη in vivo, the polι-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.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User:	Alan Lehmann
Date Deposited:	06 Feb 2012 20:37
Last Modified:	02 Apr 2012 11:41
URI:	http://srodev.sussex.ac.uk/id/eprint/27049

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