FANCD2 limits replication stress and genome instability in cells lacking BRCA2

Probing the synthetic lethal effect of FANCD2 deletion in BRCA2-deficient cells reveals independent roles of FANCD2 and BRCA2 in stabilizing stalled replication forks to maintain genome stability and promote cell survival. The tumor suppressor BRCA2 plays a key role in genome integrity by promoting...

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Bibliographic Details
Published in:Nature structural & molecular biology Vol. 23; no. 8; pp. 755 - 757
Main Authors: Michl, Johanna, Zimmer, Jutta, Buffa, Francesca M, McDermott, Ultan, Tarsounas, Madalena
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.08.2016
Nature Publishing Group
Subjects:
13
13/2
631/337/1427
631/67/1244
Antineoplastic Agents - pharmacology
Biochemistry
Biological Microscopy
BRCA2 protein
BRCA2 Protein - metabolism
Breast cancer
brief-communication
Cancer
Cancer cells
Cell Line, Tumor
Cell Survival
DNA Damage
DNA repair
DNA Replication
Fanconi Anemia Complementation Group D2 Protein - physiology
Fanconi syndrome
Fanconi's anemia
Genetic aspects
Genetic research
Genome, Human
Genomes
Genomic Instability
HEK293 Cells
Homologous recombination
Humans
Life Sciences
Membrane Biology
Phthalazines - pharmacology
Piperazines - pharmacology
Protein Structure
Replication
Structure
Tumor suppressor genes
United Kingdom
ISSN:1545-9993, 1545-9985, 1545-9985
Online Access:Get full text
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Summary:Probing the synthetic lethal effect of FANCD2 deletion in BRCA2-deficient cells reveals independent roles of FANCD2 and BRCA2 in stabilizing stalled replication forks to maintain genome stability and promote cell survival. 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.
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ISSN:1545-9993
1545-9985
1545-9985
DOI:10.1038/nsmb.3252