We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Lack of spontaneous and radiation-induced chromosome breakage at interstitial telomeric sites in murine scid cells.
- Authors
Wong, H. -P.; Mozdarani, H.; Finnegan, C.; Mcllrath, J.; Bryant, P. E.; Slijepcevic, P.
- Abstract
Interstitial telomeric sites (ITSs) in chromosomes from DNA repair-proficient mammalian cells are sensitive to both spontaneous and radiation-induced chromosome breakage. Exact mechanisms of this chromosome breakage sensitivity are not known. To investigate factors that predispose ITSs to chromosome breakage we used murine scid cells. These cells lack functional DNA-PKcs, an enzyme involved in the repair of DNA double-strand breaks. Interestingly, our results revealed lack of both spontaneous and radiation-induced chromosome breakage at ITSs found in scid chromosomes. Therefore, it is possible that increased sensitivity of ITSs to chromosome breakage is associated with the functional DNA double-strand break repair machinery. To investigate if this is the case we used scid cells in which DNA-PKcs deficiency was corrected. Our results revealed complete disappearance of ITSs in scid cells with functional DNA-PKcs, presumably through chromosome breakage at ITSs, but their unchanged frequency in positive and negative control cells. Therefore, our results indicate that the functional DNA double-strand break machinery is required for elevated sensitivity of ITSs to chromosome breakage. Interestingly, we observed significant differences in mitotic chromosome condensation between scid cells and their counterparts with restored DNA-PKcs activity suggesting that lack of functional DNA-PKcs may cause a defect in chromatin organization. Increased condensation of mitotic chromosomes in the scid background was also confirmed in vivo. Therefore, our results indicate a previously unanticipated role of DNA-PKcs in chromatin organisation, which could contribute to the lack of ITS sensitivity to chromosome breakage in murine scid cells. Copyright © 2003 S. Karger AG, Basel
- Subjects
TELOMERES; CHROMOSOMES; CHROMOSOME abnormalities; GENETIC mutation; MARMOSA; CELLS
- Publication
Cytogenetic & Genome Research, 2004, Vol 104, Issue 1-4, p131
- ISSN
1424-8581
- Publication type
Article
- DOI
10.1159/000077477