GEN1, Holliday junction 5' flap endonuclease is a protein that in humans is encoded by the GEN1 gene. [5]
GEN1, Holliday junction 5' flap endonuclease is a protein that in humans is encoded by the GEN1 gene. [5]
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].
The GEN1 endonuclease shares redundancy with the EME1/MUS81 protein complex for DNA damage repair in mammalian cells. [6] 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. [6] 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. [6]
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids.
A Holliday junction is a branched nucleic acid structure that contains four double-stranded arms joined. These arms may adopt one of several conformations depending on buffer salt concentrations and the sequence of nucleobases closest to the junction. The structure is named after Robin Holliday, the molecular biologist who proposed its existence in 1964.
Mitotic recombination is a type of genetic recombination that may occur in somatic cells during their preparation for mitosis in both sexual and asexual organisms. In asexual organisms, the study of mitotic recombination is one way to understand genetic linkage because it is the only source of recombination within an individual. Additionally, mitotic recombination can result in the expression of recessive genes in an otherwise heterozygous individual. This expression has important implications for the study of tumorigenesis and lethal recessive genes. Mitotic homologous recombination occurs mainly between sister chromatids subsequent to replication. Inter-sister homologous recombination is ordinarily genetically silent. During mitosis the incidence of recombination between non-sister homologous chromatids is only about 1% of that between sister chromatids.
DNA mismatch repair protein Mlh1 or MutL protein homolog 1 is a protein that in humans is encoded by the MLH1 gene located on chromosome 3. It is a gene commonly associated with hereditary nonpolyposis colorectal cancer. Orthologs of human MLH1 have also been studied in other organisms including mouse and the budding yeast Saccharomyces cerevisiae.
CHEK2 is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked to a wide range of cancers.
Spo11 is a protein that in humans is encoded by the SPO11 gene. Spo11, in a complex with mTopVIB, creates double strand breaks to initiate meiotic recombination. Its active site contains a tyrosine which ligates and dissociates with DNA to promote break formation. One Spo11 protein is involved per strand of DNA, thus two Spo11 proteins are involved in each double stranded break event.
Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.
DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ERCC1 gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.
Exonuclease 1 is an enzyme that in humans is encoded by the EXO1 gene.
ERCC4 is a protein designated as DNA repair endonuclease XPF that in humans is encoded by the ERCC4 gene. Together with ERCC1, ERCC4 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.
Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene.
DNA mismatch repair protein Mlh3 is a protein that in humans is encoded by the MLH3 gene.
Crossover junction endonuclease EME1 is an enzyme that in humans is encoded by the EME1 gene. It forms a complex with MUS81 which resolves Holliday junctions. In mammalian cells the EME1/MUS81 protein complex is redundant for DNA damage repair with GEN1 endonuclease. In mice, EME1/MUS81 and GEN1 redundantly contribute to Holliday junction processing. When homozygous mutations of Gen1 and Eme1 were combined in mice the result was synthetic lethality at an early embryonic stage. Homozygosity for Gen1 mutations did not cause a DNA repair deficiency in mice. But when mice were both homozygous mutant for Gen1 and also heterozyous for an Emc1 mutation, they showed increased sensitivity to DNA damaging agents. This finding, indicated a redundant role of GEN1 and EME1 in DNA repair. Gen1 and Emc1 were also shown to have redundant roles in meiotic recombination.
RecQ-mediated genome instability protein 1 is a protein that in humans is encoded by the RMI1 gene.
Fanconi anemia, complementation group M, also known as FANCM is a human gene. It is an emerging target in cancer therapy, in particular cancers with specific genetic deficiencies.
SLX4 is a protein involved in DNA repair, where it has important roles in the final steps of homologous recombination. Mutations in the gene are associated with the disease Fanconi anemia.
Crossover junction endodeoxyribonuclease, also known as Holliday junction resolvase, Holliday junction endonuclease, Holliday junction-cleaving endonuclease, Holliday junction-resolving endoribonuclease, crossover junction endoribonuclease, and cruciform-cutting endonuclease, is an enzyme involved in DNA repair and homologous recombination. Specifically, it performs endonucleolytic cleavage that results in single-stranded crossover between two homologous DNA molecules at the Holliday junction to produce recombinant DNA products for chromosomal segregation. This process is known as Holliday junction resolution.
FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease and a member of the myotubularin-related class 1 cysteine-based protein tyrosine phosphatases. It is thought to play an important role in the Fanconi Anemia (FA) pathway.
SLX4 interacting protein is a protein that in humans is encoded by the SLX4IP gene.
Testis expressed 15 is a protein that in humans is encoded by the TEX15 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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