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Title: Germline mutation rates at tandem repeat loci in DNA-repair deficient mice.
Authors: Barber, RC
Miccoli, L
van Buul PP
Burr, KL
van Duyn-Goedhart A
Angulo, JF
Dubrova, YE
First Published: 4-Oct-2004
Citation: MUTAT RES, 2004, 554 (1-2), pp. 287-295
Abstract: 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.
DOI Link: 10.1016/j.mrfmmm.2004.05.003
ISSN: 0027-5107
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Genetics

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