title: PALB2 self-interaction controls homologous recombination.
abstract: PALB2 is essential for BRCA2 anchorage to nuclear structures and for homologous recombinational repair of DNA double-strand breaks. Here, we report that the N-terminal coiled-coil motif of PALB2 regulates its self-association and homologous recombination. Monomeric PALB2 shows higher efficiency to bind DNA and promotes RAD51 filament formation with or without the inhibitory effect of Replication Protein A. Moreover, overexpression of the PALB2 coiled-coil domain severely affects RAD51 loading to DNA damage sites suggesting a competition between PALB2 self-interaction and PALB2-BRCA1 interaction. In the presence of DNA damage, the switch between PALB2-PALB2 and PALB2-BRCA1 interactions allows the activation of HR. Controlling HR via PALB2 self-interactions could be important to prevent aberrant recombination in normal conditions and activate DNA repair when required.
authors.affiliation: Genome Stability Laboratory, Laval University Cancer Research Center, Hôtel-Dieu de Québec, Québec city (Québec), G1R 2J6, Canada.
authors.forename: Rémi
authors.initials: R
authors.lastname: Buisson
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Masson
mesh_terms: D004247:DNA / Q000378:metabolism; D000076164:Fanconi Anemia Complementation Group N Protein; D057809:HEK293 Cells; D006367:HeLa Cells; D059765:Homologous Recombination; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D051135:Rad51 Recombinase / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins; D004247:DNA; D051135:Rad51 Recombinase