Deficiency of the DNA repair protein nibrin increases the basal but not the radiation induced mutation frequency in vivo

Mutation Research
Petra WessendorfMartin Digweed

Abstract

Nibrin (NBN) is a member of a DNA repair complex together with MRE11 and RAD50. The complex is associated particularly with the repair of DNA double strand breaks and with the regulation of cell cycle check points. Hypomorphic mutation of components of the complex leads to human disorders characterised by radiosensitivity and increased tumour occurrence, particularly of the lymphatic system. We have examined here the relationship between DNA damage, mutation frequency and mutation spectrum in vitro and in vivo in mouse models carrying NBN mutations and a lacZ reporter plasmid. We find that NBN mutation leads to increased spontaneous DNA damage in fibroblasts in vitro and high basal mutation rates in lymphatic tissue of mice in vivo. The characteristic mutation spectrum is dominated by single base transitions rather than the deletions and complex rearrangements expected after abortive repair of DNA double strand breaks. We conclude that in the absence of wild type nibrin, the repair of spontaneous errors, presumably arising during DNA replication, makes a major contribution to the basal mutation rate. This applies also to cells heterozygous for an NBN null mutation. Mutation frequencies after irradiation in vivo were not increas...Continue Reading

References

Nov 1, 1989·Molecular & General Genetics : MGG·H IkehataT Kato
Jan 1, 1995·Carcinogenesis·J YuanP M Glazer
Apr 29, 1997·Mutation Research·A R CollinsR Stĕtina
Jun 23, 1999·Mutation Research·M Kraakman-van der ZwetM Z Zdzienicka
Oct 26, 1999·Environmental and Molecular Mutagenesis·M E DolléJ Vijg
Jun 5, 2001·Journal of Medical Genetics·J A HielP Concannon
Dec 31, 2002·Mutation Research·Krzysztof KońcaAndrzej Wojcik
Jun 9, 2004·International Journal of Cancer. Journal International Du Cancer·Jan SteffenKarl Sperling
Apr 12, 2005·Nature Medicine·Pierre-Olivier FrappartZhao-Qi Wang
Jun 21, 2005·Nature Cell Biology·Simone DifilippantonioAndré Nussenzweig
Oct 27, 2005·International Journal of Radiation Biology·U Kasten-PisulaE Dikomey
Jan 16, 2007·Apoptosis : an International Journal on Programmed Cell Death·Daniel SaganHedda Eichholtz-Wirth
Apr 17, 2007·Nature Methods·Ana Maria GarciaJan Vijg
Aug 19, 2007·Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes·Goran GajskiVera Garaj-Vrhovac
Oct 25, 2007·International Journal of Cancer. Journal International Du Cancer·Natalia BogdanovaThilo Dörk
Dec 13, 2007·Journal of the National Cancer Institute·Eva SeemanováKarl Sperling
Apr 3, 2008·Cancer Research·Rita A BusuttilJan Vijg
May 13, 2008·DNA Repair·Allen G Schroering, Kandace J Williams
Mar 1, 2012·Orphanet Journal of Rare Diseases·Krystyna H ChrzanowskaMartin Digweed
May 12, 2012·International Journal of Oncology·Rowena Wan, David L Crowe

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Citations

Aug 13, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bastian SalewskyMartin Digweed
Dec 18, 2019·International Journal of Radiation Biology·Vinita ChauhanRobert Stainforth

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