The Tumor Suppressor PALB2: Inside Out

Trends Biochem Sci. 2019 Mar;44(3):226-240. doi: 10.1016/j.tibs.2018.10.008. Epub 2019 Jan 10.

Abstract

Partner and Localizer of BRCA2 (PALB2) has emerged as an important and versatile player in genome integrity maintenance. Biallelic mutations in PALB2 cause Fanconi anemia (FA) subtype FA-N, whereas monoallelic mutations predispose to breast, and pancreatic familial cancers. Herein, we review recent developments in our understanding of the mechanisms of regulation of the tumor suppressor PALB2 and its functional domains. Regulation of PALB2 functions in DNA damage response and repair occurs on multiple levels, including homodimerization, phosphorylation, and ubiquitylation. With a molecular emphasis, we present PALB2-associated cancer mutations and their detailed analysis by functional assays.

Keywords: DNA double-strand break repair; Fanconi anemia; cancer; homologous recombination; tumor suppressor.

Publication types

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

MeSH terms

  • Animals
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism*
  • DNA Damage / genetics
  • Fanconi Anemia / genetics
  • Fanconi Anemia / metabolism*
  • Female
  • Humans
  • Mutation / genetics
  • Ubiquitination / genetics
  • Ubiquitination / physiology

Substances

  • BRCA2 Protein
  • BRCA2 protein, human

Grant support