Recombinant Human DNA repair protein XRCC3 (XRCC3)

Function

Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the RAD51 paralog protein complex CX3 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, CX3 acts downstream of RAD51 recruitment; the complex binds predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junctions of replication forks. Involved in HJ resolution and thus in processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex and seems to involve GEN1 during mitotic cell cycle progression. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C

Subcellular Location

Nucleus; Cytoplasm; Cytoplasm, perinuclear region; Mitochondrion

Disease Association

Breast cancer (BC) : A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. [Disease susceptibility is associated with variants affecting the gene represented in this entry] | Melanoma, cutaneous malignant 6 (CMM6) : A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. [Disease susceptibility may be associated with variants affecting the gene represented in this entry. Variant p.Thr341Met has been reported to be associated with an increased risk for CMM6 (PubMed:11059748). Further studies have shown that this variant is functional in homology-directed DNA repair, and the association of XRCC3 with CMM6 has not been confirmed (PubMed:12037675, PubMed:12376526, PubMed:26137085, PubMed:26922354)]

Subunit

Interacts with RAD51C and RAD51. Part of the CX3 complex consisting of RAD51C and XRCC3; the complex has a ring-like structure arranged into a flat disk around a central channel; CX3 can interact with RAD51 in vitro. Forms a complex with FANCD2, BRCA2 and phosphorylated FANCG. Interacts with SWSAP1 and ZSWIM7; involved in homologous recombination repair. Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3

• Liu N. et al. XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages. — Mol. Cell (1998)
• PubMed: CI-6QALJ9DN355KS (APR-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Masson J.Y. et al. Identification and purification of two distinct complexes containing the five RAD51 paralogs. — Genes Dev. (2001)
• Kuschel B. et al. Variants in DNA double-strand break repair genes and breast cancer susceptibility. — Hum. Mol. Genet. (2002)
• Miller K.A. et al. RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51. — J. Biol. Chem. (2002)
• Liu N. et al. Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs in human cells. — Nucleic Acids Res. (2002)
• Miller K.A. et al. Domain mapping of the Rad51 paralog protein complexes. — Nucleic Acids Res. (2004)