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

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 sing

SUBMITTER: Wessendorf P 

PROVIDER: S-EPMC6289272 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature