The ubiquitination machinery of the Fanconi Anemia DNA repair pathway

Prog Biophys Mol Biol. 2021 Aug:163:5-13. doi: 10.1016/j.pbiomolbio.2020.09.009. Epub 2020 Oct 12.

Abstract

The Fanconi Anemia (FA) pathway maintains genome stability by preventing DNA damage from occurring when replication is blocked. Central to the FA pathway is the monoubiquitination of FANCI-FANCD2 mediated by a ubiquitin RING-E3 ligase complex called the FA core complex. Genetic mutation in any component of the FA core complex results in defective FANCI-FANCD2 monoubiquitination and phenotypes of DNA damage sensitivity, birth defects, early-onset bone marrow failure and cancer. Here, we discuss the mechanisms of the FA core complex and FANCI-FANCD2 monoubiquitination at sites of blocked replication and review our current understanding of the biological functions of these proteins in replication fork protection.

Keywords: DNA repair; FA core complex; FANCI-FANCD2; Fanconi anemia; Interstrand crosslink repair; Ubiquitination.

Publication types

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

MeSH terms

  • DNA Damage
  • DNA Repair
  • Fanconi Anemia Complementation Group D2 Protein / genetics
  • Fanconi Anemia Complementation Group D2 Protein / metabolism
  • Fanconi Anemia* / genetics
  • Humans
  • Ubiquitination

Substances

  • Fanconi Anemia Complementation Group D2 Protein