Caenorhabditis elegans BUB-3 and SAN-1/MAD3 Spindle Assembly Checkpoint Components Are Required for Genome Stability in Response to Treatment with Ionizing Radiation.
Caenorhabditis elegans BUB-3 and SAN-1/MAD3 Spindle Assembly Checkpoint Components Are Required for Genome Stability in Response to Treatment with Ionizing Radiation.
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DOI：
10.1534/g3.117.1122
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发表时间：
2017-12-04
期刊：
影响因子：
--
通讯作者：
Gartner A
中科院分区：
文献类型：
--
作者：
Bertolini S;Wang B;Meier B;Hong Y;Gartner A
关于纺锤体组装检查点和DNA损伤反应之间的串扰，特别是在多细胞生物中，所知相对较少。我们进行了秀丽隐杆线虫正向遗传筛选，以发现参与电离辐射诱导的DNA损伤修复的新基因。我们分离出一个突变gt 2000，它赋予电离辐射超敏反应，并表明gt 2000在bub-3中引入了一个过早的终止。BUB-3是主轴装配检查点的关键部件。我们提供的证据表明，BUB-3在发育过程中和生殖细胞中起作用;辐照的BUB-3（gt 2000）幼虫发育迟缓，形成异常外阴。此外，bub-3（gt 2000）胚胎从辐射蠕虫显示出增加的致死率水平。bub-3和san-1（C. MAD 3的elegans同源物）缺失等位基因赋予对电离辐射的超敏性，这与纺锤体组装检查点途径是DNA损伤反应所需的概念一致。BUB-3（GT 2000）对交联药物顺铂中等敏感，但对紫外线或甲磺酸甲酯不敏感。这与处理DNA双链断裂而不是碱基损伤的作用一致。双突变体分析显示，bub-3不参与修复双链断裂的三个主要途径中的任何一个。最后，cdc-20功能获得性突变体cdc-20/fzy-1（av 15），对纺锤体检查点引起的细胞周期延迟不敏感，表现出与bub-3和san-1突变体相似的表型。我们推测BUB-3通过调节细胞周期时间参与DNA损伤反应。
Relatively little is known about the cross-talk between the spindle assembly checkpoint and the DNA damage response, especially in multicellular organisms. We performed a Caenorhabditis elegans forward genetic screen to uncover new genes involved in the repair of DNA damage induced by ionizing radiation. We isolated a mutation, gt2000, which confers hypersensitivity to ionizing radiation and showed that gt2000 introduces a premature stop in bub-3. BUB-3 is a key component of the spindle assembly checkpoint. We provide evidence that BUB-3 acts during development and in the germline; irradiated bub-3(gt2000) larvae are developmentally retarded and form abnormal vulvae. Moreover, bub-3(gt2000) embryos sired from irradiated worms show increased levels of lethality. Both bub-3 and san-1 (the C. elegans homolog of MAD3) deletion alleles confer hypersensitivity to ionizing radiation, consistent with the notion that the spindle assembly checkpoint pathway is required for the DNA damage response. bub-3(gt2000) is moderately sensitive to the cross-linking drug cisplatin but not to ultraviolet light or methyl methanesulfonate. This is consistent with a role in dealing with DNA double-strand breaks and not with base damage. Double mutant analysis revealed that bub-3 does not act within any of the three major pathways involved in the repair of double-strand breaks. Finally, the cdc-20 gain-of-function mutant cdc-20/fzy-1(av15), which is refractory to the cell cycle delay conferred by the spindle checkpoint, showed phenotypes similar to bub-3 and san-1 mutants. We speculate that BUB-3 is involved in the DNA damage response through regulation of cell cycle timing.
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影响因子：
4.5
作者：
Bailly AP;Freeman A;Hall J;Déclais AC;Alpi A;Lilley DM;Ahmed S;Gartner A
通讯作者：
Gartner A
影响因子：
3.3
作者：
González-Huici V;Wang B;Gartner A
通讯作者：
Gartner A
影响因子：
16
作者：
Gartner, A;Milstein, S;Hengartner, MO
通讯作者：
Hengartner, MO
DOI：
10.1007/bf00267420
发表时间：
1979-01-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
CHLEBOWICZ, E;JACHYMCZYK, WJ
通讯作者：
JACHYMCZYK, WJ
DOI：
10.1016/0027-5107(90)90173-2
发表时间：
1990-07-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
BERANEK, DT
通讯作者：
BERANEK, DT