Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans.
Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans.
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DOI：
10.1186/gb-2007-8-5-r70
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Van Houten B
中科院分区：
文献类型：
--
作者：
Meyer JN;Boyd WA;Azzam GA;Haugen AC;Freedman JH;Van Houten B
线虫对UVC诱导的DNA损伤的修复在动力学和遗传学上与人类的修复相似，但在老化的线虫中修复速度显著减慢。秀丽线虫是研究衰老、神经退变和癌变等DNA损伤和修复相关过程的重要模型。然而，DNA修复在这种有机体中的特征很差。我们采用定量聚合酶链式反应的方法来表征紫外线C型(UVC)辐射对线虫DNA损伤的修复，然后测试成年线虫的DNA修复率是否受年龄的影响。UVC辐射对幼年线虫造成损伤，其斜率为每10千碱基DNA每100J/m2有0.4至0.5个损伤，在核和线粒体靶点上都是如此。L1和Dauer幼虫对病斑形成的敏感度比幼虫高5倍以上。在非妊娠成虫中，表达良好的核基因的核修复动力学是两相的：一个持续约24小时的较快的一级(半衰期约为16小时)阶段，导致大约60%的光产物被去除，随后是一个更慢的阶段。在年轻人和老年人中，10个核DNA区域的修复在转录更活跃的区域分别高出15%和50%。最后，在老年人的十个核区中，修复每个区域都减少了30%到50%。然而，修复能力的下降不能用核苷酸切除修复基因表达的减少来解释，我们提出了一个基于基因表达数据的可信机制来解释这种下降。修复紫外线诱导的线虫DNA损伤在运动学和遗传学上与人类相似。此外，这一重要的修复过程在老化的线虫中显著减慢，这是解决这个问题的第一个完整的生物体。
Repair of UVC-induced DNA damage in Caenorhabditis elegans is similar kinetically and genetically to repair in humans, and it slows significantly in aging C. elegans. Caenorhabditis elegans is an important model for the study of DNA damage and repair related processes such as aging, neurodegeneration, and carcinogenesis. However, DNA repair is poorly characterized in this organism. We adapted a quantitative polymerase chain reaction assay to characterize repair of DNA damage induced by ultraviolet type C (UVC) radiation in C. elegans, and then tested whether DNA repair rates were affected by age in adults. UVC radiation induced lesions in young adult C. elegans, with a slope of 0.4 to 0.5 lesions per 10 kilobases of DNA per 100 J/m2, in both nuclear and mitochondrial targets. L1 and dauer larvae were more than fivefold more sensitive to lesion formation than were young adults. Nuclear repair kinetics in a well expressed nuclear gene were biphasic in nongravid adult nematodes: a faster, first order (half-life about 16 hours) phase lasting approximately 24 hours and resulting in removal of about 60% of the photoproducts was followed by a much slower phase. Repair in ten nuclear DNA regions was 15% and 50% higher in more actively transcribed regions in young and aging adults, respectively. Finally, repair was reduced by 30% to 50% in each of the ten nuclear regions in aging adults. However, this decrease in repair could not be explained by a reduction in expression of nucleotide excision repair genes, and we present a plausible mechanism, based on gene expression data, to account for this decrease. Repair of UVC-induced DNA damage in C. elegans is similar kinetically and genetically to repair in humans. Furthermore, this important repair process slows significantly in aging C. elegans, the first whole organism in which this question has been addressed.
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影响因子：
10.5
作者：
Hamilton, B;Doug, YQ;Lee, SS
通讯作者：
Lee, SS
DOI：
10.1016/0921-8777(91)90050-y
发表时间：
1991-09-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
HARTMAN, P;REDDY, J;SVENDSEN, BA
通讯作者：
SVENDSEN, BA
DOI：
10.1073/pnas.76.3.1333
发表时间：
1979-01-01
影响因子：
11.1
作者：
EMMONS, SW;KLASS, MR;HIRSH, D
通讯作者：
HIRSH, D
影响因子：
3.7
作者：
Christiansen, M;Stevnsner, T;Rattan, SIS
通讯作者：
Rattan, SIS
影响因子：
16
作者：
Gartner, A;Milstein, S;Hengartner, MO
通讯作者：
Hengartner, MO