InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RAD51C

Summary

InnateDB Protein

IDBP-382374.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RAD51C

Protein Name

RAD51 homolog C (S. cerevisiae)

Synonyms

BROVCA3; FANCO; R51H3; RAD51L2;

Species

Homo sapiens

Ensembl Protein

ENSP00000391450

InnateDB Gene

IDBG-61454 (RAD51C)

Protein Structure

UniProt Annotation

Function

Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD21 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis. {ECO:0000269PubMed:14716019, ECO:0000269PubMed:16215984, ECO:0000269PubMed:16395335, ECO:0000269PubMed:19451272, ECO:0000269PubMed:19783859, ECO:0000269PubMed:20413593, ECO:0000269PubMed:23108668, ECO:0000269PubMed:23149936}.

Subcellular Localization

Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Mitochondrion. Note=DNA damage induces an increase in nuclear levels. Accumulates in DNA damage induced nuclear foci or RAD51C foci which is formed during the S or G2 phase of cell cycle. Accumulation at DNA lesions requires the presence of NBN/NBS1, ATM and RPA.

Disease Associations

Fanconi anemia complementation group O (FANCO) [MIM:613390]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269PubMed:20400963}. Note=The disease is caused by mutations affecting the gene represented in this entry.Breast-ovarian cancer, familial, 3 (BROVCA3) [MIM:613399]: A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. {ECO:0000269PubMed:20400964, ECO:0000269PubMed:21990120}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in a variety of tissues, with highest expression in testis, heart muscle, spleen and prostate.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.

Experimentally validated
Total	29 [view]
Protein-Protein	29 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0000400	four-way junction DNA binding
GO:0003677	DNA binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008094	DNA-dependent ATPase activity
GO:0008821	crossover junction endodeoxyribonuclease activity

Biological Process

GO:0000724	double-strand break repair via homologous recombination
GO:0000737	DNA catabolic process, endonucleolytic
GO:0006200	ATP catabolic process
GO:0006281	DNA repair
GO:0006310	DNA recombination
GO:0007062	sister chromatid cohesion
GO:0007596	blood coagulation
GO:0010971	positive regulation of G2/M transition of mitotic cell cycle

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005657	replication fork
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0033063	Rad51B-Rad51C-Rad51D-XRCC2 complex
GO:0033065	Rad51C-XRCC3 complex
GO:0048471	perinuclear region of cytoplasm
GO:0048476	Holliday junction resolvase complex