High impact information on RAD51C

• In addition to being critical for RAD51 focus formation, RAD51C localizes to DNA damage sites [1].
• Inhibition of RAD51C results in a decrease in cellular proliferation consistent with a role in repairing double-strand breaks (DSBs) that occur naturally [1].
• Complex formation by the human RAD51C and XRCC3 recombination repair proteins [2].
• Expression analysis in 12 primary tumors showed that RAD51C and S6K were consistently expressed in all cases in which they were amplified and also in some tumors without amplification [3].
• Here, we show that, like MLH1, RAD51C localized to mouse meiotic chromosomes at pachytene/diplotene [4].

Biological context of RAD51C

• RAD51C includes a previously mapped sequenced-tagged site location near the end of chromosome 17q [5].
• Identification of functional domains in the RAD51L2 (RAD51C) protein and its requirement for gene conversion [6].
• We report that mitotic RAD51C deficient CL-V4B cells also have an increased number of centrosomes in mitosis resulting in aberrant mitotic spindles [7].
• Increased centrosome numbers following a RAD51C defect indicates that this protein might be important in preventing aneuploidy, suggesting that it could be a potential tumour suppressor in mammals [7].
• Role of RAD51C and XRCC3 in genetic recombination and DNA repair [4].

Anatomical context of RAD51C

• The RAD51C transcript is expressed in various human tissues, with highest level of expression in testis, followed by heart muscle, spleen and prostate [5].
• Here, we confirm that the frequency of DNA double-strand break (DSB)-induced HR is reduced in the RAD51C deficient cell line CL-V4B, in agreement with a role for RAD51C in HR [7].

Physical interactions of RAD51C

• We extended these observations to examine the interaction between the RAD51B/RAD51C complex and the other RAD51 paralogs [8].
• RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51 [8].

Other interactions of RAD51C

• The RAD51B/RAD51C heterocomplex was isolated and purified by immunoaffinity chromatography from insect cells co-expressing the recombinant proteins [8].
• Six SNPs have been detected in the DNA repair genes RAD51C and RAD51D, not previously characterized [9].

Analytical, diagnostic and therapeutic context of RAD51C

• Using immunoprecipitation and gel filtration analyses, we found that Holliday junction resolvase activity associated tightly and co-eluted with the 80-kDa RAD51C-XRCC3 complex [4].
• By using site-directed mutagenesis of RAD51L2, we show that non-conservative mutation of the putative ATP-binding domain severely reduces its function, whereas a conservative mutation shows partial loss of function [6].

References