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      Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA.

      Nature genetics
      Amino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, Cloning, Molecular, DNA, genetics, DNA, Fungal, DNA-Binding Proteins, Fungal Proteins, Gene Expression, Genes, Fungal, Humans, Mice, Molecular Sequence Data, Rad51 Recombinase, Rec A Recombinases, Recombination, Genetic, Saccharomyces cerevisiae Proteins, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Homology, Amino Acid, Species Specificity

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          Abstract

          Rad51, of Saccharomyces cerevisiae, is a homologue of recA of Escherichia coli and plays crucial roles in both mitotic and meiotic recombination and in repair of double-strand breaks of DNA. We have cloned genes from human, mouse and fission yeast that are homologous to rad51. The 339 amino acid proteins predicted for the two mammalian genes are almost identical and are highly homologous (83%) with the yeast proteins. The mouse gene is transcribed at a high level in thymus, spleen, testis and ovary and at a lower level in brain and other tissues. The rad51 homologues fail to complement the DNA repair defect of rad51 mutants of S. cerevisiae. The mouse gene is located in the F1 region of chromosome 2 and the human gene maps to chromosome 15.

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          Somatic generation of antibody diversity.

          In the genome of a germ-line cell, the genetic information for an immunoglobulin polypeptide chain is contained in multiple gene segments scattered along a chromosome. During the development of bone marrow-derived lymphocytes, these gene segments are assembled by recombination which leads to the formation of a complete gene. In addition, mutations are somatically introduced at a high rate into the amino-terminal region. Both somatic recombination and mutation contribute greatly to an increase in the diversity of antibody synthesized by a single organism.
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            DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression.

            DMC1 is a new meiosis-specific yeast gene. Dmc1 protein is structurally similar to bacterial RecA proteins. dmc1 mutants are defective in reciprocal recombination, accumulate double-strand break (DSB) recombination intermediates, fail to form normal synaptonemal complex (SC), and arrest late in meiotic prophase. dmc1 phenotypes are consistent with a functional relationship between Dmc1 and RecA, and thus eukaryotic and prokaryotic mechanisms for homology recognition and strand exchange may be related. dmc1 phenotypes provide further evidence that recombination and SC formation are interrelated processes and are consistent with a requirement for DNA-DNA interactions during SC formation. dmc1 mutations confer prophase arrest. Additional evidence suggests that arrest occurs at a meiosis-specific cell cycle "checkpoint" in response to a primary defect in prophase chromosome metabolism. DMC1 is homologous to yeast's RAD51 gene, supporting the view that mitotic DSB repair has been recruited for use in meiotic chromosome metabolism.
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              • Record: found
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              Rapid and efficient site-specific mutagenesis without phenotypic selection.

              T Kunkel (1985)
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