Recruitment of DNA polymerase eta by FANCD2 in the early response to DNA damage

Cell Cycle. 2013 Mar 1;12(5):803-9. doi: 10.4161/cc.23755. Epub 2013 Feb 6.


How Fanconi anemia (FA) protein D2 (FANCD2) performs DNA damage repair remains largely elusive. We report here that translesion synthesis DNA polymerase (pol) eta is a novel mediator of FANCD2 function. We found that wild type (wt) FANCD2, not K561R (mt) FANCD2, can interact with pol eta. Upon DNA damage, the interaction of pol eta with FANCD2 occurs earlier than that with PCNA, which is in concert with our finding that FANCD2 monoubiquitination peaks at an earlier time point than that of PCNA monoubiquitination. FANCD2-null FA patient cells (PD20) carrying histone H2B-fused pol eta and wtFANCD2, respectively, show a similar tendency of low Mitomycin C (MMC) sensitivity, while cells transfected with empty vector control or pol eta alone demonstrate a similar high level of MMC sensitivity. It therefore appears that FANCD2 monoubiquitination plays a similar anchor role as histone to bind DNA in regulating pol eta. Collectively, our study indicates that, in the early phase of DNA damage response, FANCD2 plays crucial roles in recruiting pol eta to the sites of DNA damage for repair.

Keywords: DNA polymerase eta; FANCD2; PCNA; XP-V; cancer susceptibility syndrome; early DNA damage response; error-free TL; genome stability; the FA tumor suppressor pathway; translesion synthesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Chromatin / metabolism
  • DNA Damage*
  • DNA-Directed DNA Polymerase / metabolism*
  • Fanconi Anemia Complementation Group D2 Protein / chemistry
  • Fanconi Anemia Complementation Group D2 Protein / metabolism*
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Mitomycin / pharmacology
  • Models, Biological
  • Multiprotein Complexes / metabolism
  • Mutation / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Binding / drug effects
  • Protein Binding / radiation effects
  • Protein Structure, Tertiary
  • Ubiquitinated Proteins / metabolism
  • Ubiquitination / drug effects
  • Ubiquitination / radiation effects
  • Ultraviolet Rays


  • Chromatin
  • FANCD2 protein, human
  • Fanconi Anemia Complementation Group D2 Protein
  • Histones
  • Multiprotein Complexes
  • Proliferating Cell Nuclear Antigen
  • Ubiquitinated Proteins
  • Mitomycin
  • DNA-Directed DNA Polymerase
  • Rad30 protein