A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance

• Published in: EMBO reports Vol. 12; no. 7; pp. 705 - 712
• Main 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
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.07.2011; Nature Publishing Group UK; Springer Nature B.V; Nature Publishing Group
• Subjects: AURORA A/BORA/PLK1; BRCA2 Protein - genetics; BRCA2 Protein - metabolism; BRCA2-PALB2; Breast cancer; Cell Line; Deoxyribonucleic acid; DNA; DNA Damage; DNA repair; EMBO06; EMBO13; Fanconi Anemia Complementation Group N Protein; G2 checkpoint; G2 Phase - genetics; G2 Phase - physiology; Gene Library; Genomics; HCT116 Cells; HeLa Cells; High-Throughput Screening Assays; Humans; Ionizing radiation; Molecular biology; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Proteins; Recombination, Genetic; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Scientific Report; Scientific Reports; Signal Transduction - genetics; siRNA screens; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; G2 checkpoint; BRCA2–PALB2; siRNA screens; DNA damage; AURORA A/BORA/PLK1
• ISSN: 1469-221X; 1469-3178; 1469-3178
• DOI: 10.1038/embor.2011.99

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. The authors discover an essential role for the breast cancer tumour suppressors BRCA2 and PALB2 in the maintenance of the G2 checkpoint after DNA damage. The results suggest that BRCA2 and PALB2 suppress the AURORA A‐PLK1 checkpoint‐recovery pathway.