Different types of interaction between PCNA and PIP boxes contribute to distinct cellular functions of Y-family DNA polymerases

Nucleic Acids Res. 2015 Sep 18;43(16):7898-910. doi: 10.1093/nar/gkv712. Epub 2015 Jul 13.


Translesion DNA synthesis (TLS) by the Y-family DNA polymerases Polη, Polι and Polκ, mediated via interaction with proliferating cell nuclear antigen (PCNA), is a crucial pathway that protects human cells against DNA damage. We report that Polη has three PCNA-interacting protein (PIP) boxes (PIP1, 2, 3) that contribute differentially to two distinct functions, stimulation of DNA synthesis and promotion of PCNA ubiquitination. The latter function is strongly associated with formation of nuclear Polη foci, which co-localize with PCNA. We also show that Polκ has two functionally distinct PIP boxes, like Polη, whereas Polι has a single PIP box involved in stimulation of DNA synthesis. All three polymerases were additionally stimulated by mono-ubiquitinated PCNA in vitro. The three PIP boxes and a ubiquitin-binding zinc-finger of Polη exert redundant and additive effects in vivo via distinct molecular mechanisms. These findings provide an integrated picture of the orchestration of TLS polymerases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Cell Line
  • DNA / biosynthesis*
  • DNA Polymerase iota
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Humans
  • Mutation
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Interaction Domains and Motifs
  • Ubiquitination


  • Proliferating Cell Nuclear Antigen
  • DNA
  • DNA-Directed DNA Polymerase
  • POLK protein, human
  • Rad30 protein
  • DNA Polymerase iota
  • POLI protein, human