Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.
Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.
复制标题
细胞XPA和PARP-1对砷抑制和锌救援的差异敏感性。
DOI：
10.1016/j.taap.2017.05.031
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发表时间：
2017-09-15
影响因子：
3.8
通讯作者：
Liu KJ
中科院分区：
文献类型：
--
作者：
Ding X;Zhou X;Cooper KL;Huestis J;Hudson LG;Liu KJ
亚砷酸盐直接与DNA修复蛋白聚（ADP核糖）聚合酶（PARP）-1的锌指结构域结合，并抑制PARP-1在碱基切除修复（BER）途径中的活性。亚砷酸盐抑制PARP可增强紫外线辐射（UVR）诱导的角质形成细胞DNA损伤，补充锌可降低DNA损伤的增加。然而，很少有人知道砷和锌对锌指核苷酸切除修复（NER）蛋白着色性干皮病A组（XPA）的影响。在这项研究中，我们研究了XPA和PARP-1对砷暴露的反应差异，以及补锌在恢复蛋白质DNA结合和DNA损伤修复方面的差异有效性。亚砷酸盐靶向人角质形成细胞中的XPA和PARP-1，导致每种蛋白质的锌损失以及XPA和PARP-1与染色质结合的显著降低，如Chip-on-Western测定所示。当锌浓度等于亚砷酸盐浓度时，锌有效地恢复了PARP-1和XPA与染色质的DNA结合。相比之下，锌在挽救砷增强的直接UVR诱导的DNA损伤方面比氧化DNA损伤更有效。综上所述，我们的研究结果表明，亚砷酸盐干扰PARP-1和XPA与染色质的结合，并且锌补充剂完全恢复了细胞环境中两种蛋白质的DNA结合活性。有趣的是，通过补充锌对亚砷酸盐抑制的DNA损伤修复的拯救对于通过XPA相关的NER途径修复的DNA损伤比PARP-1依赖的BER途径更敏感。这项研究扩展了我们对亚砷酸盐在DNA修复抑制和共致癌作用中的理解。
Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)- induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA). In this study, we investigated the difference in response to arsenite exposure between XPA and PARP-1, and the differential effectiveness of zinc supplementation in restoring protein DNA binding and DNA damage repair. Arsenite targeted both XPA and PARP-1 in human keratinocytes, resulting in zinc loss from each protein and a pronounced decrease in XPA and PARP-1 binding to chromatin as demonstrated by Chip-on-Western assays. Zinc effectively restored DNA binding of PARP-1 and XPA to chromatin when zinc concentrations were equal to those of arsenite. In contrast, zinc was more effective in rescuing arsenite-augmented direct UVR- induced DNA damage than oxidative DNA damage. Taken together, our findings indicate that arsenite interferes with PARP-1 and XPA binding to chromatin, and that zinc supplementation fully restores DNA binding activity to both proteins in the cellular context. Interestingly, rescue of arsenite- inhibited DNA damage repair by supplemental zinc was more sensitive for DNA damage repaired by the XPA-associated NER pathway than for the PARP-1-dependent BER pathway. This study expands our understanding of arsenite’s role in DNA repair inhibition and co-carcinogenesis.
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影响因子：
4.1
作者：
Qin, Xu-Jun;Hudson, Laurie G.;Liu, Wenlan;Ding, Wei;Cooper, Karen L.;Liu, Ke Han
通讯作者：
Liu, Ke Han
影响因子：
--
作者：
Aguilar-Quesada R;Muñoz-Gámez JA;Martín-Oliva D;Peralta A;Valenzuela MT;Matínez-Romero R;Quiles-Pérez R;Menissier-de Murcia J;de Murcia G;Ruiz de Almodóvar M;Oliver FJ
通讯作者：
Oliver FJ
影响因子：
4.8
作者：
Ding, Wei;Liu, Wenlan;Liu, Ke Jian
通讯作者：
Liu, Ke Jian
影响因子：
4.2
作者：
Ho, E;Courtemanche, C;Ames, BN
通讯作者：
Ames, BN
影响因子：
3.8
作者：
Cooper, Karen L.;King, Brenee S.;Sandoval, Monica M.;Liu, Ke Jian;Hudson, Laurie G.
通讯作者：
Hudson, Laurie G.