DNA repair protein XRCC3 is a protein that in humans is encoded by the XRCC3 gene. [5]
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 functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [6]
The XRCC3 protein is one of five 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. [7]
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. [8]
Two paralogs form a complex designated CX3 (RAD51C-XRCC3). Four paralogs form a second complex designated BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2). These two complexes act at two different stages of homologous recombinational DNA repair.
The CX3 complex acts downstream of RAD51, after its recruitment to damage sites. [8] The CX3 complex associates with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts. [8]
The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites. [8] The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament.
XRCC3 has been shown to interact with RAD51C. [9] [10] [11] [12]
There is an epigenetic cause of XRCC3 deficiency that appears to increase cancer risk. This is the repression of XRCC3 by over-expression of EZH2 protein.
Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC3, and thus reduces homologous recombinational repair. [13] This reduction was proposed to be a cause of breast cancer. [13] 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. [14] EZH2 protein is up-regulated in numerous cancers. [14] [15] 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. [16]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
XRCC3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | XRCC3, CMM6, X-ray repair complementing defective repair in Chinese hamster cells 3, X-ray repair cross complementing 3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 600675 MGI: 1921585 HomoloGene: 36178 GeneCards: XRCC3 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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DNA repair protein XRCC3 is a protein that in humans is encoded by the XRCC3 gene. [5]
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 functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [6]
The XRCC3 protein is one of five 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. [7]
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. [8]
Two paralogs form a complex designated CX3 (RAD51C-XRCC3). Four paralogs form a second complex designated BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2). These two complexes act at two different stages of homologous recombinational DNA repair.
The CX3 complex acts downstream of RAD51, after its recruitment to damage sites. [8] The CX3 complex associates with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts. [8]
The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites. [8] The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament.
XRCC3 has been shown to interact with RAD51C. [9] [10] [11] [12]
There is an epigenetic cause of XRCC3 deficiency that appears to increase cancer risk. This is the repression of XRCC3 by over-expression of EZH2 protein.
Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC3, and thus reduces homologous recombinational repair. [13] This reduction was proposed to be a cause of breast cancer. [13] 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. [14] EZH2 protein is up-regulated in numerous cancers. [14] [15] 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. [16]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]