Novel RNA and DNA strand exchange activity of the PALB2 DNA binding domain and its critical role for DNA repair in cells

Elife. 2019 Apr 29:8:e44063. doi: 10.7554/eLife.44063.

Abstract

BReast Cancer Associated proteins 1 and 2 (BRCA1, -2) and Partner and Localizer of BRCA2 (PALB2) protein are tumour suppressors linked to a spectrum of malignancies, including breast cancer and Fanconi anemia. PALB2 coordinates functions of BRCA1 and BRCA2 during homology-directed repair (HDR) and interacts with several chromatin proteins. In addition to protein scaffold function, PALB2 binds DNA. The functional role of this interaction is poorly understood. We identified a major DNA-binding site of PALB2, mutations in which reduce RAD51 foci formation and the overall HDR efficiency in cells by 50%. PALB2 N-terminal DNA-binding domain (N-DBD) stimulates the function of RAD51 recombinase. Surprisingly, it possesses the strand exchange activity without RAD51. Moreover, N-DBD stimulates the inverse strand exchange and can use DNA and RNA substrates. Our data reveal a versatile DNA interaction property of PALB2 and demonstrate a critical role of PALB2 DNA binding for chromosome repair in cells.

Keywords: DNA recombination; DNA repair; E. coli; biochemistry; cancer biology; chemical biology; human; protein-DNA interaction; tumor supressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • DNA / metabolism*
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fanconi Anemia Complementation Group N Protein / genetics
  • Fanconi Anemia Complementation Group N Protein / metabolism*
  • Humans
  • RNA / metabolism*
  • Recombination, Genetic*

Substances

  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group N Protein
  • PALB2 protein, human
  • RNA
  • DNA

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.