Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability Journal Article


Authors: Richardson, C.; Stark, J. M.; Ommundsen, M.; Jasin, M.
Article Title: Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability
Abstract: Genomic instability is characteristic of tumor cells, and a strong correlation exists between abnormal karyotype and tumorigenicity. Increased expression of the homologous recombination and DNA repair protein Rad51 has been reported in immortalized and tumor cells, which could alter recombination pathways to contribute to the chromosomal rearrangements found in these cells. We used a genetic system to examine the potential for multiple double-strand breaks to lead to genome rearrangements in the presence of increased Rad51 expression. Analysis of repair revealed a novel class of products consistent with crossing over, involving gene conversion associated with an exchange of flanking markers leading to chromosomal translocations. Increased Rad51 also promoted aneuploidy and multiple chromosomal rearrangements. These data provide a link between elevated Rad51 protein levels, genome instability, and tumor progression.
Keywords: controlled study; protein expression; human cell; dna-binding proteins; nonhuman; genetic analysis; neoplasms; animal cell; mouse; dna damage; homologous recombination; in situ hybridization, fluorescence; dna repair; gene expression; embryo; protein stability; animalia; gene conversion; double stranded dna; recombination, genetic; genomic instability; disease progression; data analysis; chromosome translocation; translocation, genetic; genome; dna flanking region; tumor growth; aneuploidy; genetic linkage; rad51 protein; gene structure; rad51 recombinase; translocation; cross linking; crossover; system analysis; dna double-strand break; rad51; humans; human; priority journal; article; genome instability
Journal Title: Oncogene
Volume: 23
Issue: 2
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 2004-01-15
Start Page: 546
End Page: 553
Language: English
DOI: 10.1038/sj.onc.1207098
PROVIDER: scopus
PUBMED: 14724582
DOI/URL:
Notes: Oncogene -- Cited By (since 1996):111 -- Export Date: 16 June 2014 -- CODEN: ONCNE -- Source: Scopus
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  1. Jeremy M Stark
    8 Stark
  2. Maria Jasin
    249 Jasin