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DNA-PKcs is critical for telomere capping [electronic resource].

Published:
Washington, D.C. : United States. Dept. of Energy, 2001.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy.
Additional Creators:
United States. Department of Energy, National Science Foundation (U.S.), and United States. Department of Energy. Office of Scientific and Technical Information
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Summary:
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is critical for DNA repair via the non-homologous end joining (NHEJ) pathway. Previously, it was reported that bone marrow cells and spontaneously transformed fibroblasts from SCID (severe combined immunodeficiency) mice have defects in telomere maintenance. The genetically defective SCID mouse arose spontaneously from its parental strain CB17. One known genomic alteration in SCID mice is a truncation of the extreme carboxyl-terminus of DNA-PKcs, but other as yet unidentified alterations may also exist. We have used a defined system, the DNA-PKcs knockout mouse, to investigate specifically the role DNA-PKcs specifically plays in telomere maintenance. We report that primary mouse embryonic fibroblasts (MEFs) and primary cultured kidney cells from 6-8 month old DNA-PKcs deficient mice accumulate a large number of telomere fusions, yet still retain wildtype telomere length. Thus, the phenotype of this defect separates the two-telomere related phenotypes, capping and length maintenance. DNA-PKcs deficient MEFs also exhibit elevated levels of chromosome fragments and breaks, which correlate with increased telomere fusions. Based on the high levels of telomere fusions observed in DNA-PKcs deficient cells, we conclude that DNA-PKcs plays an important capping role at the mammalian telomere.
Report Numbers:
E 1.99:lbnl--47731
lbnl--47731
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Published through SciTech Connect.
04/10/2001.
"lbnl--47731"
": KP1102020"
Proceedings of the National Academy of Sciences USA 98 26 FT
Kurimasa,Akihiro; Hande, M. Prakash; Chen, David J.; Gilley, David; Li, Gloria C.; Tanaka, Hiromi.
Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
Radiological Society of NorthAmerica SD#0029, Japanese Society for the Promotion ofScience
Funding Information:
DE-AC02-05CH11231
NIHAG17709
444001
View MARC record | catkey: 13811682