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{sup -/-}) deficient male mice. Non-exposed scid and PARP{sup -/-} 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{sup -/-} 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{sup -/-} 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{sup -/-} 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{sup -/-} can be explained by the high cell killing effects of irradiation on the germline of deficient mice.
Citation Formats
Barber, Ruth C, Miccoli, Laurent, Buul, Paul P.W. van, Burr, Karen L.-A., Duyn-Goedhart, Annemarie van, Angulo, Jaime F, and Dubrova, Yuri E.
Germline mutation rates at tandem repeat loci in DNA-repair deficient mice.
Netherlands: N. p.,
2004.
Web.
doi:10.1016/j.mrfmmm.2004.05.003.
Barber, Ruth C, Miccoli, Laurent, Buul, Paul P.W. van, Burr, Karen L.-A., Duyn-Goedhart, Annemarie van, Angulo, Jaime F, & Dubrova, Yuri E.
Germline mutation rates at tandem repeat loci in DNA-repair deficient mice.
Netherlands.
https://doi.org/10.1016/j.mrfmmm.2004.05.003
Barber, Ruth C, Miccoli, Laurent, Buul, Paul P.W. van, Burr, Karen L.-A., Duyn-Goedhart, Annemarie van, Angulo, Jaime F, and Dubrova, Yuri E.
2004.
"Germline mutation rates at tandem repeat loci in DNA-repair deficient mice."
Netherlands.
https://doi.org/10.1016/j.mrfmmm.2004.05.003.
@misc{etde_20618300,
title = {Germline mutation rates at tandem repeat loci in DNA-repair deficient mice}
author = {Barber, Ruth C, Miccoli, Laurent, Buul, Paul P.W. van, Burr, Karen L.-A., Duyn-Goedhart, Annemarie van, Angulo, Jaime F, and Dubrova, Yuri E}
abstractNote = {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{sup -/-}) deficient male mice. Non-exposed scid and PARP{sup -/-} 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{sup -/-} 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{sup -/-} 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{sup -/-} 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{sup -/-} can be explained by the high cell killing effects of irradiation on the germline of deficient mice.}
doi = {10.1016/j.mrfmmm.2004.05.003}
journal = []
issue = {1-2}
volume = {554}
journal type = {AC}
place = {Netherlands}
year = {2004}
month = {Oct}
}
title = {Germline mutation rates at tandem repeat loci in DNA-repair deficient mice}
author = {Barber, Ruth C, Miccoli, Laurent, Buul, Paul P.W. van, Burr, Karen L.-A., Duyn-Goedhart, Annemarie van, Angulo, Jaime F, and Dubrova, Yuri E}
abstractNote = {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{sup -/-}) deficient male mice. Non-exposed scid and PARP{sup -/-} 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{sup -/-} 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{sup -/-} 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{sup -/-} 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{sup -/-} can be explained by the high cell killing effects of irradiation on the germline of deficient mice.}
doi = {10.1016/j.mrfmmm.2004.05.003}
journal = []
issue = {1-2}
volume = {554}
journal type = {AC}
place = {Netherlands}
year = {2004}
month = {Oct}
}