Proliferating cell nuclear antigen-dependent coordination of the biological functions of human DNA polymerase

Antonio E. Vidal, Patricia Kannouche, Vladimir N. Podust, Wei Yang, Alan R. Lehmann, Roger Woodgate

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    80 Citations (Scopus)

    Résumé

    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 poli 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.

    langue originaleAnglais
    Pages (de - à)48360-48368
    Nombre de pages9
    journalJournal of Biological Chemistry
    Volume279
    Numéro de publication46
    Les DOIs
    étatPublié - 12 nov. 2004

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