Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / pharmacology
-
BRCA2 Protein / metabolism*
-
Cell Line, Tumor
-
Cell Survival
-
DNA Damage
-
DNA Replication
-
Fanconi Anemia Complementation Group D2 Protein / physiology*
-
Genome, Human
-
Genomic Instability
-
HEK293 Cells
-
Humans
-
Phthalazines / pharmacology
-
Piperazines / pharmacology
Substances
-
Antineoplastic Agents
-
BRCA2 Protein
-
BRCA2 protein, human
-
FANCD2 protein, human
-
Fanconi Anemia Complementation Group D2 Protein
-
Phthalazines
-
Piperazines
-
olaparib