title: A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance.
abstract: To identify key connections between DNA-damage repair and checkpoint pathways, we performed RNA interference screens for regulators of the ionizing radiation-induced G2 checkpoint, and we identified the breast cancer gene BRCA2. The checkpoint was also abrogated following depletion of PALB2, an interaction partner of BRCA2. BRCA2 and PALB2 depletion led to premature checkpoint abrogation and earlier activation of the AURORA A-PLK1 checkpoint-recovery pathway. These results indicate that the breast cancer tumour suppressors and homologous recombination repair proteins BRCA2 and PALB2 are main regulators of G2 checkpoint maintenance following DNA-damage.
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen N 2200, Denmark.
authors.forename: Tobias
authors.initials: T
authors.lastname: Menzel
authors.forename: Viola
authors.initials: V
authors.lastname: Nähse-Kumpf
authors.forename: Arne Nedergaard
authors.initials: AN
authors.lastname: Kousholt
authors.forename: Ditte Kjærsgaard
authors.initials: DK
authors.lastname: Klein
authors.forename: Christin
authors.initials: C
authors.lastname: Lund-Andersen
authors.forename: Michael
authors.initials: M
authors.lastname: Lees
authors.forename: Jens Vilstrup
authors.initials: JV
authors.lastname: Johansen
authors.forename: Randi G
authors.initials: RG
authors.lastname: Syljuåsen
authors.forename: Claus Storgaard
authors.initials: CS
authors.lastname: Sørensen
mesh_terms: D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D000076164:Fanconi Anemia Complementation Group N Protein; D016195:G2 Phase / Q000235:genetics / Q000502:physiology*; D015723:Gene Library; D045325:HCT116 Cells; D006367:HeLa Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D024682:BRCA2 Protein; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins