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.
Mesh Terms:
Amino Acid Sequence, Binding Sites, DNA Replication, DNA-Binding Proteins, DNA-Directed DNA Polymerase, Enzyme Activation, Humans, Macromolecular Substances, Models, Molecular, Proliferating Cell Nuclear Antigen, Protein Binding, Protein Structure, Tertiary, Recombinant Fusion Proteins, Replication Protein A, Replication Protein C, Sequence Alignment, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Nov. 12, 2004
Download Curated Data For This Publication
134783
Switch View:
  • Interactions 3