A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance |
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Authors: | Menzel Tobias Nähse-Kumpf Viola Kousholt Arne Nedergaard Klein Ditte Kjærsgaard Lund-Andersen Christin Lees Michael Johansen Jens Vilstrup Syljuåsen Randi G Sørensen Claus Storgaard |
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Institution: | 1. Biotech Research and Innovation Centre, University of Copenhagen, , Copenhagen, N 2200 Denmark;2. Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, , Oslo, 0310 Norway |
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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. |
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Keywords: | siRNA screens G2 checkpoint DNA damage BRCA2–PALB2 AURORA A/BORA/PLK1 |
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