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

J Biol Chem. 2004 Nov 12;279(46):48360-8. doi: 10.1074/jbc.M406511200. Epub 2004 Sep 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • DNA Polymerase iota
  • DNA Replication*
  • DNA-Binding Proteins / metabolism
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Enzyme Activation
  • Humans
  • Macromolecular Substances
  • Models, Molecular
  • Proliferating Cell Nuclear Antigen / chemistry
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Replication Protein A
  • Replication Protein C
  • Sequence Alignment
  • Two-Hybrid System Techniques


  • DNA-Binding Proteins
  • Macromolecular Substances
  • Proliferating Cell Nuclear Antigen
  • RPA1 protein, human
  • Recombinant Fusion Proteins
  • Replication Protein A
  • DNA-Directed DNA Polymerase
  • Replication Protein C
  • DNA Polymerase iota
  • POLI protein, human