A new X-ray sensitive CHO cell mutant of ionizing radiation group 7, XR-C2, that is defective in DSB repair but has only a mild defect in V(D)J recombination

Autor: Errami, A, Overkamp, W.J.I, He, D.M, Friedl, A.A, Gell, D.A, Eckardt-Schupp, F, Jackson, S.P, Hendrickson, E.A, Lohman, P.H.M, Zdzienicka, M.Z
Zdroj: Mutation Research/DNA Repair; September 2000, Vol. 461 Issue: 1 p59-69, 11p
Abstrakt: The DNA-dependent protein kinase (DNA-PK) complex plays a key role in DNA double-strand break (DSB) repair and V(D)J recombination. Using a genetic approach we have isolated cell mutants sensitive to ionizing radiation (IR) in the hope of elucidating the mechanism and components required for these pathways. We describe here, an X-ray-sensitive and DSB repair defective Chinese hamster ovary (CHO) cell line, XR-C2, which was assigned to the X-Ray Cross Complementation (XRCC) group 7. This group of mutants is defective in the XRCC7/SCID/Prkdcgene, which encodes the catalytic subunit of DNA-PK (DNA-PKcs). Despite the fact that XR-C2 cells expressed normal levels of DNA-PKcs protein, no DNA-PK catalytic activity could be observed in XR-C2, confirming the genetic analyses that these cells harbor a dysfunctional gene for DNA-PKcs. In contrast to other IR group 7 mutants, which contain undetectable or low levels of DNA-PKcs protein and which show a severe defect in V(D)J recombination, XR-C2 cells manifested only a mild defect in both coding and signal junction formation. The unique phenotype of the XR-C2 mutant suggests that a normal level of kinase activity is critical for radiation resistance but not for V(D)J recombination, whereas the overall structure of the DNA-PKcs protein appears to be of great importance for this process.
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