Proliferating cell nuclear antigen-dependent coordination of the biological functions of human DNA polymerase iota.
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 eta (poleta), 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 iota (poliota) and the proliferating cell nuclear antigen (PCNA) stimulates the processivity of poliota in a template-dependent manner in vitro. Mutations in one of the putative PCNA-binding motifs (PIP box) of poliota or the interdomain connector loop of PCNA diminish the binding between poliota and PCNA and concomitantly reduce PCNA-dependent stimulation of poliota activity. Furthermore, although retaining its capacity to interact with poleta in vivo, the poliota-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.
Vidal
Antonio E
AE
Laboratory of Genomic Integrity, NICHD, National Institutes of Health, Bethesda, Maryland 20892-2725, USA.
Kannouche
Patricia
P
Podust
Vladimir N
VN
Yang
Wei
W
Lehmann
Alan R
AR
Woodgate
Roger
R
D000595:Amino Acid Sequence; D001665:Binding Sites; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051716:Replication Protein A; D051818:Replication Protein C; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D000094769:DNA Polymerase iota
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D018809:Proliferating Cell Nuclear Antigen; C497167:RPA1 protein, human; D011993:Recombinant Fusion Proteins; D051716:Replication Protein A; D004259:DNA-Directed DNA Polymerase; D051818:Replication Protein C; D000094769:DNA Polymerase iota; C000722070:POLI protein, human