FANCD2 limits replication stress and genome instability in cells lacking BRCA2.
The tumor suppressor BRCA2 plays a key role in genome integrity by promoting replication-fork stability and homologous recombination (HR) DNA repair. Here we report that human cancer cells lacking BRCA2 rely on the Fanconi anemia protein FANCD2 to limit replication-fork progression and genomic instability. Our results identify a new role of FANCD2 in limiting constitutive replication stress in BRCA2-deficient cells, thereby affecting cell survival and treatment responses.
The CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, U.K.
Johanna
J
Michl
The CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, U.K.
Jutta
J
Zimmer
The CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, U.K.
Francesca M
FM
Buffa
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Ultan
U
McDermott
The CR-UK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, U.K.
Madalena
M
Tarsounas
D000970:Antineoplastic Agents / Q000494:pharmacology; D024682:BRCA2 Protein / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004249:DNA Damage; D004261:DNA Replication; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000502:physiology*; D015894:Genome, Human; D042822:Genomic Instability; D057809:HEK293 Cells; D006801:Humans; D010793:Phthalazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology
D000970:Antineoplastic Agents; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D010793:Phthalazines; D010879:Piperazines; C531550:olaparib