XRCC2

XRCC2
Identifiers
Aliases	XRCC2, FANCU, X-ray repair cross complementing 2, SPGF50, POF17
External IDs	OMIM: 600375 MGI: 1927345 HomoloGene: 3964 GeneCards: XRCC2
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q36.1 Start 152,644,776 bp[1] End 152,676,141 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 B1 Start 25,894,810 bp[2] End 25,910,823 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in external globus pallidus sperm pylorus subthalamic nucleus inferior ganglion of vagus nerve cardia ventral tegmental area superior surface of tongue renal medulla pericardium Top expressed in spermatocyte cumulus cell yolk sac secondary oocyte spermatid renal corpuscle abdominal wall seminiferous tubule otic placode primitive streak More reference expression data BioGPS 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 Species Human Mouse Entrez 7516 57434 Ensembl ENSG00000196584 ENSMUSG00000028933 UniProt O43543 Q9CX47 RefSeq (mRNA) NM_005431 NM_020570 RefSeq (protein) NP_005422 NP_065595 Location (UCSC) Chr 7: 152.64 – 152.68 Mb Chr 5: 25.89 – 25.91 Mb PubMed search [3] [4]
Wikidata
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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]

References

Further reading