UV-induced histone H2AX phosphorylation and DNA damage related proteins accumulate and persist in nucleotide excision repair-deficient XP-B cells.
UV-induced histone H2AX phosphorylation and DNA damage related proteins accumulate and persist in nucleotide excision repair-deficient XP-B cells.
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DOI：
10.1016/j.dnarep.2010.09.004
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发表时间：
2011-01-02
期刊：
影响因子：
3.8
通讯作者：
Kraemer KH
中科院分区：
文献类型：
--
作者：
Oh KS;Bustin M;Mazur SJ;Appella E;Kraemer KH
DNA双链断裂（DSB）可能由电离辐射引起。相比之下，UV暴露形成二嘧啶光产物，并且不被认为是DSB的诱导物。我们发现，均匀或局部紫外线处理诱导的DNA损伤相关（DDR）蛋白H2 AX，ATM和NBS 1的磷酸化和γ-H2 AX与DDR蛋白p-ATM，p-NBS 1，Rad 51和FANCD 2的共定位，持续约6小时在正常人成纤维细胞。在不存在核苷酸切除修复（NER）的情况下观察到这种UV后磷酸化，因为NER缺陷型XP-B细胞（缺乏功能性XPB DNA修复解旋酶）和全局基因组修复缺陷型啮齿动物细胞也显示这些DDR蛋白的磷酸化和定位。DDR蛋白的分辨率依赖于NER，因为它们在XP-B细胞中持续24小时。在正常和XP-B细胞中，在6 h和24 h检测到p53和p21，但在XP-B细胞中未诱导Mdm 2。在正常细胞中检测到UV诱导后的Wip 1磷酸酶，但在XP-B细胞中未检测到。用中性彗星试验检测正常和XP-B细胞在紫外线照射后6 h和24 h的DNA双链断裂。这些结果表明，紫外线损伤可以激活DDR途径在NER的情况下。然而，在NER的情况下，没有观察到涉及诱导Wip 1和DDR蛋白的分辨率的DNA损伤处理的后续步骤。
DNA double strand breaks (DSB) may be caused by ionizing radiation. In contrast, UV exposure forms dipyrimidine photoproducts and is not considered an inducer of DSB. We found that uniform or localized UV treatment induced phosphorylation of the DNA damage related (DDR) proteins H2AX, ATM and NBS1 and co-localization of γ-H2AX with the DDR proteins p-ATM, p-NBS1, Rad51 and FANCD2 that persisted for about 6 h in normal human fibroblasts. This post-UV phosphorylation was observed in the absence of nucleotide excision repair (NER), since NER deficient XP-B cells (lacking functional XPB DNA repair helicase) and global genome repair-deficient rodent cells also showed phosphorylation and localization of these DDR proteins. Resolution of the DDR proteins was dependent on NER, since they persisted for 24 h in the XP-B cells. In the normal and XP-B cells p53 and p21 was detected at 6 h and 24 h but Mdm2 was not induced in the XP-B cells. Post-UV induction of Wip1 phosphatase was detected in the normal cells but not in the XP-B cells. DNA DSB were detected with a neutral comet assay at 6 h and 24 h post-UV in the normal and XP-B cells. These results indicate that UV damage can activate the DDR pathway in the absence of NER. However, a later step in DNA damage processing involving induction of Wip1 and resolution of DDR proteins was not observed in the absence of NER.
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影响因子：
11.2
作者：
Alekseev, S;Kool, H;Mullenders, LHF
通讯作者：
Mullenders, LHF
DOI：
10.1073/pnas.0603779103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Marti, Thomas M.;Hefner, Eli;Cleaver, James E.
通讯作者：
Cleaver, James E.
DOI：
10.1073/pnas.94.12.6048
发表时间：
1997-06-10
影响因子：
11.1
作者：
Fiscella, M;Zhang, HL;Appella, E
通讯作者：
Appella, E
DOI：
10.1073/pnas.1002175107
发表时间：
2010-04-13
影响因子：
11.1
作者：
de Feraudy, Sebastien;Revet, Ingrid;Cleaver, James E.
通讯作者：
Cleaver, James E.
影响因子：
11.4
作者：
Bogliolo, Massimo;Lyakhovich, Alex;Surralles, Jordi
通讯作者：
Surralles, Jordi