XRCC2

XRCC2
Identifiers
Aliases	XRCC2, FANCU, X-ray repair cross complementing 2, SPGF50, POF17
External IDs	OMIM: 600375; MGI: 1927345; HomoloGene: 3964; GeneCards: XRCC2; OMA:XRCC2 - orthologs
Gene location (Human)
Chr.	Chromosome 7 (human)
End	152,676,141 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	25,910,823 bp
RNA expression pattern
	Top expressed in
	buccal mucosa cell; ; tendon of biceps brachii; ; external globus pallidus; ; sperm; ; pylorus; ; subthalamic nucleus; ; inferior ganglion of vagus nerve; ; pars reticulata; ; cardia; ; ventral tegmental area;
	Top expressed in
	spermatocyte; ; cumulus cell; ; ventricular zone; ; yolk sac; ; secondary oocyte; ; lumbar subsegment of spinal cord; ; spermatid; ; epiblast; ; tail of embryo; ; primary oocyte;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	DNA binding; ATP-dependent activity, acting on DNA; DNA strand exchange activity; single-stranded DNA binding; protein binding; four-way junction DNA binding; double-stranded DNA binding; endodeoxyribonuclease activity; ATP binding;
Cellular component	cytoplasm; centrosome; replication fork; microtubule organizing center; Rad51B-Rad51C-Rad51D-XRCC2 complex; cytoskeleton; nucleus; nucleoplasm; intracellular membrane-bounded organelle;
Biological process	somitogenesis; response to ionizing radiation; strand invasion; negative regulation of neuron apoptotic process; reciprocal meiotic recombination; neurogenesis; DNA recombination; multicellular organism growth; regulation of fibroblast apoptotic process; in utero embryonic development; cellular response to DNA damage stimulus; positive regulation of neurogenesis; mitotic cell cycle; mitotic recombination; response to gamma radiation; DNA repair; response to X-ray; meiotic DNA recombinase assembly; double-strand break repair via homologous recombination; meiosis; centrosome cycle;
	Sources:Amigo / QuickGO
Orthologs
	7516
	57434
	ENSG00000196584
	ENSMUSG00000028933
	O43543
	Q9CX47
	NM_005431
	NM_020570
	NP_005422
	NP_065595
	Wikidata
View/Edit Human	View/Edit Mouse

DNA repair protein XRCC2 is a protein that in humans is encoded by the XRCC2 gene.^[5]^[6]^[7]

Function

This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents.^[7]

The XRCC2 protein is one of five human paralogs of RAD51, including RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 and XRCC3. They each share about 25% amino acid sequence identity with RAD51 and each other.^[8]

The RAD51 paralogs are all required for efficient DNA double-strand break repair by homologous recombination and depletion of any paralog results in significant decreases in homologous recombination frequency.^[9]

XRCC2 forms a four-part complex with three related paralogs: BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2) while two paralogs form a second complex CX3 (RAD51C-XRCC3). These two complexes act at two different stages of homologous recombinational DNA repair. The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.^[9] The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament.

The CX3 complex acts downstream of RAD51 recruitment to damage sites.^[9] The CX3 complex was shown to associate with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts.^[9]

Interactions

XRCC2 has been shown to interact with RAD51L3,^[10]^[11]^[12]^[13] Bloom syndrome protein^[11] and RAD51C.^[13]^[14]

Epigenetic deficiency in cancer

There are two known epigenetic causes of XRCC2 deficiency that appear to increase cancer risk. These are methylation of the XRCC2 promoter and epigenetic repression of XRCC2 by over-expression of EZH2 protein.

The XRCC2 gene was found to be hypermethylated in the promoter region in 52 of 54 cases of cervical cancer.^[15] Promoter hypermethylation reduces gene expression, and thus would reduce the tumor suppressing homologous recombinational repair otherwise supported by XRCC2.

Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC2, and thus reduces homologous recombinational repair.^[16] This reduction was proposed to be a cause of breast cancer.^[16] EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization.^[17] EZH2 protein is up-regulated in numerous cancers.^[17]^[18] EZH2 mRNA is up-regulated, on average, 7.5-fold in breast cancer, and between 40% and 75% of breast cancers have over-expressed EZH2 protein.^[19]