GEN1, Holliday junction 5' flap endonuclease

GEN1, Holliday junction 5' flap endonuclease is a protein that in humans is encoded by the GEN1 gene.

GEN1
Identifiers
Aliases	GEN1, Gen, Holliday junction 5' flap endonuclease, GEN1 Holliday junction 5' flap endonuclease
External IDs	OMIM: 612449; MGI: 2443149; HomoloGene: 35313; GeneCards: GEN1; OMA:GEN1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2p24.2 Start 17,753,858 bp End 17,788,946 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12|12 A1.1 Start 11,288,921 bp End 11,315,802 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle bone marrow cells gonad endothelial cell epithelium of nasopharynx ventricular zone pancreatic ductal cell tonsil appendix rectum Top expressed in tail of embryo genital tubercle zygote lumbar spinal ganglion yolk sac secondary oocyte maxillary prominence embryo ventricular zone epiblast More reference expression data BioGPS n/a
Gene ontology Molecular function crossover junction endodeoxyribonuclease activity DNA binding nuclease activity endonuclease activity catalytic activity hydrolase activity metal ion binding endodeoxyribonuclease activity magnesium ion binding four-way junction DNA binding 5'-flap endonuclease activity protein homodimerization activity double-stranded DNA binding single-stranded DNA binding single-stranded DNA 3'-5' exodeoxyribonuclease activity double-stranded DNA 3'-5' exodeoxyribonuclease activity single-stranded DNA 5'-3' exodeoxyribonuclease activity flap endonuclease activity double-stranded DNA 5'-3' exodeoxyribonuclease activity 5'-3' exodeoxyribonuclease activity Cellular component centrosome nucleus nucleoplasm Biological process resolution of recombination intermediates positive regulation of mitotic cell cycle spindle assembly checkpoint regulation of centrosome duplication resolution of mitotic recombination intermediates nucleic acid phosphodiester bond hydrolysis cellular response to DNA damage stimulus DNA repair double-strand break repair via homologous recombination replication fork processing DNA catabolic process, endonucleolytic DNA catabolic process, exonucleolytic UV-damage excision repair Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 348654 209334 Ensembl ENSG00000178295 ENSMUSG00000051235 UniProt Q17RS7 Q8BMI4 RefSeq (mRNA) NM_001130009 NM_182625 NM_177331 RefSeq (protein) NP_001123481 NP_872431 NP_796305 Location (UCSC) Chr 2: 17.75 – 17.79 Mb Chr 12: 11.29 – 11.32 Mb PubMed search
Wikidata
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Function

This gene encodes a member of the Rad2/xeroderma pigmentosum group G nuclease family, whose members are characterized by N-terminal and internal xeroderma pigmentosum group G nuclease domains followed by helix-hairpin-helix domains and disordered C-terminal domains. The protein encoded by this gene is involved in resolution of Holliday junctions, which are intermediate four-way structures that covalently link DNA during homologous recombination and double-strand break repair. The protein resolves Holliday junctions by creating dual incisions across the junction to produce nicked duplex products that can be ligated. In addition, this protein has been found to localize to centrosomes where it has been implicated in regulation of centrosome integrity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016].

Redundancy with EME1/MUS81

The GEN1 endonuclease shares redundancy with the EME1/MUS81 protein complex for DNA damage repair in mammalian cells. GEN1 and EME1/MUS81, in mice, have redundant functions with respect to their contributions to Holliday junction processing. When mice had homozygous mutations for both Gen1 and Eme1, they exhibited synthetic lethality at an early embryonic stage. Gen1 mutant homozygosity, alone, in mice did not cause a DNA repair deficiency. However, if mice homozygous for mutant Gen1 were also heterozyous for an Emc1 mutation, they displayed elevated sensitivity to DNA damaging agents. These observations indicated that GEN1 and EME1 have redundant roles in DNA repair. Gen1 and Emc1 also appear to have redundant roles in meiotic recombination.

Further reading

• Ip SC, Rass U, Blanco MG, Flynn HR, Skehel JM, West SC (2008). "Identification of Holliday junction resolvases from humans and yeast". Nature. 456 (7220): 357–61. Bibcode:2008Natur.456..357I. doi:10.1038/nature07470. PMID 19020614. S2CID 4362699.
• Lorenz A, West SC, Whitby MC (2010). "The human Holliday junction resolvase GEN1 rescues the meiotic phenotype of a Schizosaccharomyces pombe mus81 mutant". Nucleic Acids Res. 38 (6): 1866–73. doi:10.1093/nar/gkp1179. PMC 2847240. PMID 20040574.
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Mol. Med. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
• Turnbull C, Hines S, Renwick A, Hughes D, Pernet D, Elliott A, Seal S, Warren-Perry M, Gareth Evans D, Eccles D, Stratton MR, Rahman N (2010). "Mutation and association analysis of GEN1 in breast cancer susceptibility". Breast Cancer Res. Treat. 124 (1): 283–8. doi:10.1007/s10549-010-0949-1. PMC 3632835. PMID 20512659.
• Turnbull C, Hines S, Renwick A, Hughes D, Pernet D, Elliott A, Seal S, Warren-Perry M, Gareth Evans D, Eccles D, Stratton MR, Rahman N (2010). "Mutation and association analysis of GEN1 in breast cancer susceptibility". Breast Cancer Res. Treat. 124 (1): 283–8. doi:10.1007/s10549-010-0949-1. PMC 3632835. PMID 20512659.
• Liu Y, Shete S, Wang LE, El-Zein R, Etzel CJ, Liang FW, Armstrong G, Tsavachidis S, Gilbert MR, Aldape KD, Xing J, Wu X, Wei Q, Bondy ML (2010). "Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk". Carcinogenesis. 31 (10): 1762–9. doi:10.1093/carcin/bgq141. PMC 2981459. PMID 20610542.
• Rass U, Compton SA, Matos J, Singleton MR, Ip SC, Blanco MG, Griffith JD, West SC (2010). "Mechanism of Holliday junction resolution by the human GEN1 protein". Genes Dev. 24 (14): 1559–69. doi:10.1101/gad.585310. PMC 2904945. PMID 20634321.
• Flachsbart F, Franke A, Kleindorp R, Caliebe A, Blanché H, Schreiber S, Nebel A (2010). "Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study". Mutat. Res. 694 (1–2): 13–9. doi:10.1016/j.mrfmmm.2010.08.006. PMID 20800603.
• Rodrigue A, Coulombe Y, Jacquet K, Gagné JP, Roques C, Gobeil S, Poirier G, Masson JY (2013). "The RAD51 paralogs ensure cellular protection against mitotic defects and aneuploidy". J. Cell Sci. 126 (Pt 1): 348–59. doi:10.1242/jcs.114595. PMID 23108668.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.