Structure-Function Relationship of DNA Repair Proteins: Lessons from BRCA1 and RAD51 Studies

Boutou, Effrossyni; Pappa, Vassiliki; Stuerzbecher, Horst-Werner; Vorgias, Constantinos E.

doi:10.5772/24605

Cited by 1 publication

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“…BRCA2 contains nuclear localization signals not found in RAD51, supporting the notion that BRCA2 also facilitates RAD51 transport into the nucleus. The direct interactions of RAD51 and BRCA1 have not yet been fully elucidated, despite gene expression profiling and network modeling revealing a complex heterogeneity in the mechanisms of BRCA1 involvement in tumorigenesis [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Loss of heterozygosity for chromosomal regions 15q14-21.1, 17q21.31, and 13q12.3-13.1 and its relevance for prostate cancer

et al. 2015

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Although prostate cancer is one of the most common cancers in men, the genetic defects underlying its pathogenesis remain poorly understood. DNA damage repair mechanisms have been implicated in human cancer. Accumulating evidence indicates that the fidelity of the response to DNA double-strand breaks is critical for maintaining genome integrity. RAD51 is a central player in double-strand break repair via homologous recombination, and its alterations may confer and increase the risk of cancer. RAD51 functioning depends on the indirect or direct interactions with BRCA1 and BRCA2. To evaluate the contribution of RAD51 to sporadic prostate cancer, loss of heterozygosity (LOH) for chromosomal region 15q14-21.1 (RAD51locus) was determined and compared to LOH in 17q21.31 (BRCA1 locus) and 13q12.3-13.1 (BRCA2 region). DNA was isolated from prostate biopsies and matched peripheral blood of 50 patients. The regions 15q14-21.1, 17q21.31, and 13q12.3-13.1 were examined using microsatellite markers on chromosome 15 (D15S118, D15S214, D15S1006), chromosome 17 (D17S855, D17S1323), and chromosome 13 (D13S260, D13S290), respectively. The LOH in tumors was analyzed by PCR with fluorescently labeled primers and an ABI PRISM 377 DNA Sequencer. Allele sizing was determined by GeneScan version 3.1.2 and Genotyper version 2.5 software (Applied Biosystems, USA). LOH was identified in 57.5, 23, and 40 % for chromosomal regions 15q14-21.1, 17q21.31, and 13q12.3-13.1, respectively. Twenty-six percent of studied cases manifested LOH for at least one marker in 15q14-21.1 exclusively. A significant correlation was found between LOH for studied region and PSAD (prostate-specific antigen density). The findings suggest that RAD51 may be considered as a prostate cancer susceptibility gene.

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Section: Introductionmentioning

confidence: 99%