Understanding BRCA2 Function as a Tumor Suppressor Based on Domain-Specific Activities in DNA Damage Responses
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Division of Experimental Hematology and Cancer Biology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
2
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
3
Department of Otorhinolaryngology and Head/Neck Surgery, Heinrich Heine University, 40225 Düsseldorf, Germany
4
Department of Pediatrics III, Children’s Hospital, University of Duisburg-Essen, 45122 Essen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Devilee
Genes 2021, 12(7), 1034; https://doi.org/10.3390/genes12071034
Received: 30 April 2021
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Revised: 23 June 2021
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Accepted: 29 June 2021
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Published: 2 July 2021
(This article belongs to the Special Issue BRCA1 and BRCA2: Genome Instability and Tumorigenesis)
BRCA2 is an essential genome stability gene that has various functions in cells, including roles in homologous recombination, G2 checkpoint control, protection of stalled replication forks, and promotion of cellular resistance to numerous types of DNA damage. Heterozygous mutation of BRCA2 is associated with an increased risk of developing cancers of the breast, ovaries, pancreas, and other sites, thus BRCA2 acts as a classic tumor suppressor gene. However, understanding BRCA2 function as a tumor suppressor is severely limited by the fact that ~70% of the encoded protein has not been tested or assigned a function in the cellular DNA damage response. Remarkably, even the specific role(s) of many known domains in BRCA2 are not well characterized, predominantly because stable expression of the very large BRCA2 protein in cells, for experimental purposes, is challenging. Here, we review what is known about these domains and the assay systems that are available to study the cellular roles of BRCA2 domains in DNA damage responses. We also list criteria for better testing systems because, ultimately, functional assays for assessing the impact of germline and acquired mutations identified in genetic screens are important for guiding cancer prevention measures and for tailored cancer treatments.
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Keywords:
BRCA2; tumor suppressor; DNA damage responses; DNA repair; homologous recombination; G2 checkpoint; DNA binding; variants of uncertain significance
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MDPI and ACS Style
Andreassen, P.R.; Seo, J.; Wiek, C.; Hanenberg, H. Understanding BRCA2 Function as a Tumor Suppressor Based on Domain-Specific Activities in DNA Damage Responses. Genes 2021, 12, 1034. https://doi.org/10.3390/genes12071034
AMA Style
Andreassen PR, Seo J, Wiek C, Hanenberg H. Understanding BRCA2 Function as a Tumor Suppressor Based on Domain-Specific Activities in DNA Damage Responses. Genes. 2021; 12(7):1034. https://doi.org/10.3390/genes12071034
Chicago/Turabian StyleAndreassen, Paul R., Joonbae Seo, Constanze Wiek, and Helmut Hanenberg. 2021. "Understanding BRCA2 Function as a Tumor Suppressor Based on Domain-Specific Activities in DNA Damage Responses" Genes 12, no. 7: 1034. https://doi.org/10.3390/genes12071034
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