Nucleic Acids Research, Vol 25, Issue 15 2985-2991, Copyright © 1997 by Oxford University Press
Y Xiao and DT Weaver
Repair of DNA damage resulting in double-strand breaks (DSBs) is controlled
by gene products executing homologous recombination or end- joining
pathways. The MRE11 gene has previously been implicated in DSB repair in
the yeast Saccharomyces cerevisiae . Here we have developed a methodology
to study the roles of the murine Mre11 homolog in pluripotent embryonic
stem cells. Using a gene targeting approach, a triple LoxP site cassette
was inserted into a region of MRE11 genomic DNA flanking conserved
phosphodiesterase motifs. The addition of Cre recombinase activity promotes
deletions of three types that can be scored. We find that deletion at
phosphodiesterase motif III encoded in the N-terminus of Mre11 is acheived
in the presence of a wild-type MRE11 allele. However, when the wild-type
MRE11 allele is inactivated by gene targeted insertion of a neo marker,
only Cre recombination events that allow expression of wild-type Mre11
protein are observed. Therefore, Mre11 is required for normal cell
proliferation. This methodology introduces a means to study important
regions of essential genes in cell culture models.
ARTICLES
Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells
Department of Microbiology and Molecular Genetics, Harvard Medical School and Division of Tumor Immunology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
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