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标题：Increase in Telomere Sequence-Binding Activity in Normal Human Fibroblasts in Senescence or in Cells Treated with Phorbol Ester or N-Methyl-N'-nitro-N-nitrosoguanidine
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作者：Kiyoshi NOSE ; Keiko ISHINO ; Motoko SHIBANUMA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1998
卷号：21
期号：9
页码：911-913
DOI：10.1248/bpb.21.911
出版社：The Pharmaceutical Society of Japan
摘要：The telomere is a specialized chromatin structure composed of unique repetitive DNA sequences and specific nuclear proteins. Telomere sequence-binding activity was measured by a mobility shift assay using nuclear extract from normal human fibroblasts. The specific binding activity to the telomere sequence increased in cells that were in a senscence state compared to that in cells at early population doublings. Treatment of cells with tumor promoting phorbol ester TPA induced an increase in the telomere sequence binding activity of nuclear extract in young cells, but the increase was marginal in senescent cells. DNA-damaging N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) also increased the telomere sequence binding activity in young cells, but not in senescent cells. As a reference, we measured the binding activity to NFkB sequence. It was activated by TPA or okadaic acid, but was not affected by MNNG or in senescence. The increase in telomere sequence-binding activity seemed to depend on activation of tyrosine phosphorylation, since an inhibitor of Tyr-kinase abolished the increase in telomere-binding activity. The molecular weight of the major binding factor in the normal human fibroblasts was approximately 32 kDa which is different from that of the telomere-associated protein, TRF-1.
关键词：telomere;semnescence;binding factor;alkylating agent