Cloning the RAD51 homologue of<i>Schizosaccharomyces pombe</i>

Muris, D. F. R.; Vreeken, Kees; Carr, Antony; Broughton, Bernard C.; Lehmann, Alan R.; Lohman, P.H.M.; Pastink, Albert

doi:10.1093/nar/21.19.4586

Cited by 155 publications

(93 citation statements)

References 38 publications

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“…rad13 is the S. pombe homolog of S. cerevisiae RAD2, a classical NER gene. rhp51 (21,29,46) is the S. pombe homolog of S. cerevisiae RAD51 which is thought to be involved in homologous pairing during recombination (52). Mammalian homologs of S. pombe rad2, and by implication rad2 itself, encode a structure-specific nuclease involved in DNA replication and/or repair (16,31,38;see Discussion).…”

Section: Resultsmentioning

confidence: 99%

“…rhp51 is the homolog of the S. cerevisiae RAD51 gene (29,46). The Rad51 protein forms a nucleoprotein filament with DNA as an early intermediate in recombination (47).…”

Section: Discussionmentioning

confidence: 99%

“…Some of these are involved in checkpoint control of the cell cycle to radiation (2, 3, 41). Others, which are particularly sensitive to ionizing radiation, are deficient in recombination repair (6,29,33,54). No mutant which is sensitive to ionizing but not to UV irradiation has yet been identified.…”

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confidence: 99%

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The rad18 Gene of Schizosaccharomyces pombe Defines a New Subgroup of the SMC Superfamily Involved in DNA Repair

Lehmann

Walicka

Griffiths

et al. 1995

Molecular and Cellular Biology

201

255

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The rad18 mutant of Schizosaccharomyces pombe is very sensitive to killing by both UV and ␥ radiation. We have cloned and sequenced the rad18 gene and isolated and sequenced its homolog from Saccharomyces cerevisiae, designated RHC18. The predicted Rad18 protein has all the structural properties characteristic of the SMC family of proteins, suggesting a motor function-the first implicated in DNA repair. Gene deletion shows that both rad18 and RHC18 are essential for proliferation. Genetic and biochemical analyses suggest that the product of the rad18 gene acts in a DNA repair pathway for removal of UV-induced DNA damage that is distinct from classical nucleotide excision repair. This second repair pathway involves the products of the rhp51 gene (the homolog of the RAD51 gene of S. cerevisiae) and the rad2 gene.Cells of all organisms have evolved an intricate series of DNA repair pathways to counteract the deleterious effects of all types of DNA damage. In Escherichia coli, nucleotide excision repair (NER) of UV damage requires the products of six genes. A complex of the UvrA and UvrB proteins binds to DNA and translocates to the site of the damage. The UvrC product then attaches to the complex, displacing UvrA, and the damaged DNA strand is nicked on both sides of the damaged site. The helicase activity of the UvrD product releases the oligonucleotide containing the damage, and DNA polymerase I and ligase complete the repair process (24). In eukaryotes, NER requires considerably more gene products, most of which are highly conserved (20). In Saccharomyces cerevisiae, the products of the RAD1, -2, -3, -4, -10, -14, and -25 genes are absolutely required for excision repair of UV damage, whereas there is only a partial requirement for RAD7, -16, and -23. There is evidence that the products of many of these genes form a multisubunit complex (e.g., see reference 53). In Schizosaccharomyces pombe, genes encoding highly homologous proteins have been identified (9,10,30,39), demonstrating the conservation of the classical NER pathway in this yeast.Null mutations in the S. cerevisiae NER genes RAD1, -2, -3, -10, and -14 result in a total deficiency in excision repair of UV-induced cyclobutane dimers and 6-4 photoproducts (28). Null mutants of the S. pombe homologs of RAD1 and RAD2 (rad16 and rad13, respectively), while showing many properties expected of excision repair-deficient mutants, are still able to excise UV-induced cyclobutane dimers and 6-4 photoproducts at a significant rate (7, 27). These results suggest that, in contrast to S. cerevisiae, there is a second pathway in S. pombe for removal of UV photoproducts.Most of the rad mutants of S. pombe are sensitive to both UV and ␥ irradiation. Some of these are involved in checkpoint control of the cell cycle to radiation (2, 3, 41). Others, which are particularly sensitive to ionizing radiation, are deficient in recombination repair (6,29,33,54). No mutant which is sensitive to ionizing but not to UV irradiation has yet been identified. The S. pombe rad18-X mutant ...

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Section: Resultsmentioning

confidence: 99%

“…rhp51 is the homolog of the S. cerevisiae RAD51 gene (29,46). The Rad51 protein forms a nucleoprotein filament with DNA as an early intermediate in recombination (47).…”

Section: Discussionmentioning

confidence: 99%

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The rad18 Gene of Schizosaccharomyces pombe Defines a New Subgroup of the SMC Superfamily Involved in DNA Repair

Lehmann

Walicka

Griffiths

et al. 1995

Molecular and Cellular Biology

201

255

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“…Arrowhead in (k) points to allantois. White and black bars are 200 mm and 100 mm, respectively Brca1 117/7 embryos are sensitive to g-irradiation It is known that BRCA1 and Rad51, a homolog of E. coli RecA that is involved in DNA damage repair (Muris et al, 1993;Shinohara et al, 1992Shinohara et al, , 1993, colocalize in the cell nucleus and interact with each other (Scully et al, 1997b). Since Rad51 7/7 embryos were hypersensitive to g-irradiation (Lim and Hasty, 1996), we predicted that Brca1 117/7 embryos might have a similar phenotype if these two genes interact in vivo.…”

Section: Figurementioning

confidence: 99%

“…The human Brca1 gene encodes a nuclear protein of 1863 amino acids which was recently shown to colocalize and co-immunoprecipitate with RAD 51, a homolog of E. Coli RecA that is involved in DNA damage repair (Muris et al, 1993;Scully et al, 1997a,b;Shinohara et al, 1993Shinohara et al, , 1992. Upon treatment with reagents that damage DNA, BRCA1 becomes phosphorylated and relocates to intranuclear structures in which DNA replication is taking place (Scully et al, 1997a).…”

Section: Introductionmentioning

confidence: 99%

A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability

et al. 1998

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Germline mutations of the Brca1 gene are responsible for most cases of familial breast and ovarian cancers, but somatic mutations are rarely detected in sporadic events. Moreover, mouse embryos de®cient for Brca1 have been shown to die during early embryogenesis due to a proliferation defect. These ®ndings seem incompatible with the tumor suppress function assigned to this gene and raise questions about the mechanism by which Brca1 mutations cause tumorigenesis. We now directly demonstrate that BRCA1 is responsible for the integrity of the genome. Murine embryos carrying a Brca1 null mutation are developmentally retarded and hypersensitive to girradiation, suggesting a failure in DNA damage repair. This notion is supported by spectral karyotyping (SKY) of metaphase chromosomes, which display numerical and structural aberrations. However, massive chromosomal abnormalities are only observed when a p53 7/7 background is introduced. Thus, a p53 dependent cell cycle checkpoint arrests the mutant embryos and prevents the accumulation of damaged DNA. Brca1 7/7 ®broblasts are not viable, nor are Brca1 7/7 : p53 7/7 ®broblasts. However, proliferative foci arise from Brca1 7/7 : p53 7/7 cells, probably due to additional mutations that are a consequence of the accumulating DNA damage. We believe that the increased incidence of such additional mutations accounts for the mechanism of tumorigenesis associated with Brca1 mutations in humans.

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The differentiated and conserved roles of Swi5‐Sfr1 in homologous recombination

2017

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Homologous recombination (HR) is the process whereby two DNA molecules that share high sequence similarity are able to recombine to generate hybrid DNA molecules. Throughout evolution, the ability of HR to identify highly similar DNA sequences has been adopted for numerous biological phenomena including DNA repair, meiosis, telomere maintenance, ribosomal DNA amplification and immunological diversity. Although Rad51 and Dmc1 are the key proteins that promote HR in mitotic and meiotic cells, respectively, accessory proteins that allow Rad51 and Dmc1 to effectively fulfil their functions have been identified in all examined model systems. In this Review, we discuss the roles of the highly conserved Swi5‐Sfr1 accessory complex in yeast, mice and humans, and explore similarities and differences between these species.

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Cloning the RAD51 homologue ofSchizosaccharomyces pombe

Cited by 155 publications

References 38 publications

The rad18 Gene of Schizosaccharomyces pombe Defines a New Subgroup of the SMC Superfamily Involved in DNA Repair

The rad18 Gene of Schizosaccharomyces pombe Defines a New Subgroup of the SMC Superfamily Involved in DNA Repair

A targeted disruption of the murine Brca1 gene causes γ-irradiation hypersensitivity and genetic instability

The differentiated and conserved roles of Swi5‐Sfr1 in homologous recombination

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