BRCA gene structure and function in tumor suppression: A repair-centric perspective Journal Article
| Authors: | Murphy, C. G.; Moynahan, M. E. |
| Article Title: | BRCA gene structure and function in tumor suppression: A repair-centric perspective |
| Abstract: | Germline mutations in the BRCA1 and BRCA2 genes are characterized by deficient repair of DNA double-strand breaks by homologous recombination. Defective DNA double-strand break repair has been not only implicated as a key contributor to tumorigenesis in mutation carriers but also represents a potential target for therapy. The transcriptional similarities between BRCA1-deficient tumors and sporadic tumors of the basal-like subtype have led to the investigation of homologous recombination repair-directed therapy in triple-negative tumors, which demonstrates overlap with the basal-like subtype. We broaden the scope of this topic by addressing a "repair-defective" rather than "BRCA1-like" phenotype. We discuss structural and functional aspects of key repair proteins including BRCA1, BRCA2, BRCA1 interacting protein C-terminal helicase 1, and partner and localizer of BRCA2 and describe the phenotypic consequences of their loss at the cellular, tissue, and organism level. We review potential mechanisms of repair pathway dysfunction in sporadic tumors and address how the identification of such defects may guide the application of repair-directed therapies. © 2010 Lippincott Williams & Wilkins, Inc. |
| Keywords: | gene mutation; review; nonhuman; protein function; protein localization; phenotype; allele; dna damage; homologous recombination; dna repair; breast cancer; carboxy terminal sequence; clinical assessment; gene function; protein interaction; enzyme activity; breast neoplasms; brca1 protein; brca2 protein; carcinogenesis; nibrin; dna strand breakage; cancer genetics; cancer inhibition; chromosome aberration; double stranded dna; gene rearrangement; breast tumor; dna double-strand break repair; genetic stability; genome; tissue level; helicase; cell level; brca1; brca2; germ-line mutation; genes, tumor suppressor; heterozygote detection; rad51 protein; gene structure; fanconi anemia; genetic instability; brip1; palb2; organism |
| Journal Title: | The Cancer Journal |
| Volume: | 16 |
| Issue: | 1 |
| ISSN: | 1528-9117 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2010-01-01 |
| Start Page: | 39 |
| End Page: | 47 |
| Language: | English |
| DOI: | 10.1097/PPO.0b013e3181cf0204 |
| PUBMED: | 20164689 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "CODEN: CAJOC" - "Source: Scopus" |
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