Gene-specific repair of gamma-ray-induced DNA strand breaks in colon cancer cells: no coupling to transcription and no removal from the mitochondrial genome.

Gene-specific repair of gamma-ray-induced DNA strand breaks in colon cancer cells: no coupling to transcription and no removal from the mitochondrial genome.
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结肠癌细胞中伽马射线诱导的 DNA 链断裂的基因特异性修复:不与转录偶联,也不从线粒体基因组中去除。

DOI:
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发表时间:
2000
期刊:
Biochemical and Biophysical Research Communications - BBRC
影响因子:
--
通讯作者:
V. Bohr
V. Bohr
中科院分区:
--
文献类型:
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作者:
A. May;V. Bohr

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我们测量了基因特异性DNA损伤和修复碱敏感位点和DNA链断裂后,γ射线照射。尽管为了引入足够的DNA损伤而使用了相当高的剂量,但我们发现在2小时内存在有效且几乎完全的修复。将人类结肠癌细胞暴露于γ射线照射,并在各个核区域和线粒体基因组中测量修复。在必需的管家基因二氢叶酸还原酶(DHFR)中,2 h后约有80%的链断裂修复。DHFR基因的两条DNA链之间的修复活性没有差异,因此没有证据表明修复过程存在链偏好或转录偶联。有没有优先修复的DHFR基因相比,在一个无活性的,X-连锁,非编码基因的修复。因此,我们不能检测到这些病变的形成和修复的任何核异质性。相比之下,γ射线照射引起的损伤的形成和处理在线粒体DNA中不同。在这里,我们检测到约两倍以上的碱敏感位点和γ射线照射后的链断裂比观察到的DHFR基因。这些损伤的修复在线粒体中是有缺陷的,其中只有约25%在2小时内被去除。
We have measured gene-specific DNA damage and repair of alkaline-sensitive sites and DNA strand breaks after gamma-irradiation. Although fairly high doses are used in order to introduce sufficient DNA damage, we find that there is efficient and almost complete repair within 2 h. Human colon cancer cells were exposed to gamma-irradiation, and the repair was measured in various nuclear regions and in the mitochondrial genome. In the essential housekeeping gene, dihydrofolate reductase (DHFR), there was about 80% repair of the strand breaks after 2 h. There was no difference in the repair activities between the two individual DNA strands of the DHFR gene, and thus no evidence of strand bias, or transcription coupling of the repair process. There was no preferential repair of the DHFR gene compared to repair in an inactive, X-linked, noncoding gene. We can thus not detect any nuclear heterogeneity of the formation and repair of these lesions. In contrast, the formation and processing of gamma-irradiation introduced lesions differ in the mitochondrial DNA. Here, we detect about twofold more alkaline-sensitive sites and strand breaks after gamma-irradiation than observed in the DHFR gene. The repair of these lesions is deficient in the mitochondria, where only about 25% are removed within 2 h.
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DOI: --
发表时间: 1991
期刊: The Journal of biological chemistry
影响因子: --
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