Mechanisms of recombination between diverged sequences in wild-type and BLM-deficient mouse and human cells Journal Article


Authors: LaRocque, J. R.; Jasin, M.
Article Title: Mechanisms of recombination between diverged sequences in wild-type and BLM-deficient mouse and human cells
Abstract: Double-strand breaks (DSBs) are particularly deleterious DNA lesions for which cells have developed multiple mechanisms of repair. One major mechanism of DSB repair in mammalian cells is homologous recombination (HR), whereby a homologous donor sequence is used as a template for repair. For this reason, HR repair of DSBs is also being exploited for gene modification in possible therapeutic approaches. HR is sensitive to sequence divergence, such that the cell has developed ways to suppress recombination between diverged ("homeologous") sequences. In this report, we have examined several aspects of HR between homeologous sequences in mouse and human cells. We found that gene conversion tracts are similar for mouse and human cells and are generally ≤100 bp, even in Msh2-/- cells which fail to suppress homeologous recombination. Gene conversion tracts are mostly unidirectional, with no observed mutations. Additionally, no alterations were observed in the donor sequences. While both mouse and human cells suppress homeologous recombination, the suppression is substantially less in the transformed human cells, despite similarities in the gene conversion tracts. BLM-deficient mouse and human cells suppress homeologous recombination to a similar extent as wild-type cells, unlike Sgs1-deficient Saccharomyces cerevisiae. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Keywords: controlled study; gene mutation; human cell; sequence analysis; nonhuman; animal cell; mouse; mammalia; animals; mice; mice, knockout; homologous recombination; dna repair; cell line; animal experiment; wild type; gene conversion; donor; molecular sequence data; saccharomyces cerevisiae; cell transformation; recombination, genetic; gene repression; dna breaks, double-stranded; base sequence; recq helicases; muts homolog 2 protein; bloom syndrome helicase; melanotroph; base pair mismatch
Journal Title: Molecular and Cellular Biology
Volume: 30
Issue: 8
ISSN: 0270-7306
Publisher: American Society for Microbiology  
Date Published: 2010-04-01
Start Page: 1887
End Page: 1897
Language: English
DOI: 10.1128/mcb.01553-09
PUBMED: 20154148
PROVIDER: scopus
PMCID: PMC2849462
DOI/URL:
Notes: --- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "CODEN: MCEBD" - "Source: Scopus"
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MSK Authors
  1. Maria Jasin
    250 Jasin
  2. Jeannine Larocque Kappas
    6 Kappas