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Publication : Germline mutation rates at tandem repeat loci in DNA-repair deficient mice.

First Author  Barber RC Year  2004
Journal  Mutat Res Volume  554
Issue  1-2 Pages  287-95
PubMed ID  15450426 Mgi Jnum  J:93788
Mgi Id  MGI:3505684 Doi  10.1016/j.mrfmmm.2004.05.003
Citation  Barber RC, et al. (2004) Germline mutation rates at tandem repeat loci in DNA-repair deficient mice. Mutat Res 554(1-2):287-95
abstractText  Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of non-exposed and irradiated severe combined immunodeficient (scid) and poly(ADP-ribose) polymerase (PARP-1-/-) deficient male mice. Non-exposed scid and PARP-/- male mice showed considerably elevated ESTR mutation rates, far higher than those in wild-type isogenic mice and other inbred strains. The irradiated scid and PARP-1-/- male mice did not show any detectable increases in their mutation rate, whereas significant ESTR mutation induction was observed in the irradiated wild-type isogenic males. ESTR mutation spectra in the scid and PARP-1-/- strains did not differ from those in the isogenic wild-type strains. Considering these data and the results of previous studies, we propose that a delay in repair of DNA damage in scid and PARP-1-/- mice could result in replication fork pausing which, in turn, may affect ESTR mutation rate in the non-irradiated males. The lack of mutation induction in irradiated scid and PARP-1-/- can be explained by the high cell killing effects of irradiation on the germline of deficient mice.
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