Disease relevance of RAD51L3

• The variant E233G of the RAD51D gene could be a low-penetrance allele in high-risk breast cancer families without BRCA1/2 mutations [1].
• The self-reliant system for alternative care of diabetes mellitus patients--experience macrobiotic management in Trad Province [2].
• Eight different inactivating germline mutations in the RAD51D gene were found to be associated with significantly (6 fold) increased risk of ovarian cancer [3].

High impact information on RAD51L3

• Telomere maintenance requires the RAD51D recombination/repair protein [4].
• It associates with RAD51D and ablating its expression reduces the number of RAD51 foci [5].
• These findings support a crucial role for mammalian RAD51D in normal development, recombination, and maintaining mammalian genome stability [6].
• We show that the RAD51L3-XRCC2 complex stimulates BLM to disrupt synthetic 4-way junctions that model the Holliday junction [7].
• RESULTS: TRAD induced selective E1A and E1B expression in human cancer cells, but not in normal cells such as human fibroblasts [8].

Biological context of RAD51L3

• Given the requirements for XRCC2 in genetic recombination and protection against DNA-damaging agents, we suggest that the complex of RAD51L3 and XRCC2 is likely to be important for these functions in human cells [9].
• Six SNPs have been detected in the DNA repair genes RAD51C and RAD51D, not previously characterized [1].
• By radiation hybrid mapping, the human ortholog RAD51D was mapped to chromosome 17q11, which is a region syntenic to mouse Chromosome 11 [10].
• 2% similarity with the mouse TRAD gene and had two nucleotide binding consensus sequences, motif A and motif B, conserved among members of this family [11].
• The protein expression of XRCC2, as well as its binding partner RAD51D, is dramatically increased in S- and G2-phases, suggesting that these proteins function during and after DNA synthesis [12].

Anatomical context of RAD51L3

• Ectopic expression of wild-type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line [13].
• TRAD replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human fibroblasts lacking telomerase activity [8].

Other interactions of RAD51L3

• Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D) [7].
• By using purified proteins, we demonstrate that the interaction between RAD51L3 and XRCC2 is direct [9].
• HR also plays a role in the maintenance of eukaryotic telomeres; cells defective in the recombinational repair proteins RAD51D or RAD54 exhibit telomere shortening and end-to-end chromosome fusions [14].

Analytical, diagnostic and therapeutic context of RAD51L3

• Using immunofluorescence labeling, electron microscopy, and chromatin immunoprecipitation assays, RAD51D was shown to localize to the telomeres of both meiotic and somatic cells [4].
• Northern blot analysis revealed that multiple transcripts of the human TRAD gene were expressed in various tissues and their distribution was not ubiquitous [11].
• In nu/nu mice carrying s.c. human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth [8].

References