Cellular deficiency of Werner syndrome protein or RECQ1 promotes genotoxic potential of hydroquinone and benzo[a]pyrene exposure.
Cellular deficiency of Werner syndrome protein or RECQ1 promotes genotoxic potential of hydroquinone and benzo[a]pyrene exposure.
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沃纳综合征蛋白或 RECQ1 的细胞缺陷会促进氢醌和苯并[a]芘暴露的潜在遗传毒性。
DOI：
10.1177/1091581814547422
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发表时间：
2014-09
影响因子：
2.2
通讯作者：
Sharma S
中科院分区：
文献类型：
--
作者：
Garige M;Sharma S
人类已知的5种RecQ解旋酶（RECQ1、BLM、WRN、RECQL4和RECQ5）在多种基因组维持机制中发挥作用，但它们在保护基因组免受环境毒物侵害方面的功能尚不清楚。在这里，我们评估了WRN（在Werner综合征中突变）和RECQ1 （WRN最丰富的同源物）在对苯二酚和苯并芘诱导的遗传毒性中的潜在作用。在HeLa细胞中，沉默WRN或RECQ1的表达增加了它们对对苯二酚和苯并[a]芘的敏感性，但引起了不同的DNA损伤反应。与对照或wrn -缺失细胞相比，暴露于苯并[a]芘处理后，recq1缺失细胞表现出RPA磷酸化、Chk1激活和DNA双链断裂增加。在recq1缺失细胞中，苯并[a]芘诱导的双链断裂依赖于DNA-PK活性。值得注意的是，在recq1缺失的细胞中，WRN的缺失改善了苯并[a]芘的毒性。总的来说，我们的研究结果首次表明，WRN和RECQ1在防止苯并[a]芘和对苯二酚的潜在致癌作用中发挥了非冗余作用。
The five known RecQ helicases in humans (RECQ1, BLM, WRN, RECQL4, and RECQ5) have demonstrated roles in diverse genome maintenance mechanisms but their functions in safeguarding the genome from environmental toxicants are poorly understood. Here, we have evaluated a potential role of WRN (mutated in Werner Syndrome) and RECQ1 (the most abundant homolog of WRN) in hydroquinone and benzo[a]pyrene-induced genotoxicity. Silencing of WRN or RECQ1 expression in HeLa cells increased their sensitivity to hydroquinone and benzo[a]pyrene but elicited distinct DNA damage response. RECQ1-depleted cells exhibited increased RPA phosphorylation, Chk1 activation, and DNA double strand breaks as compared to control or WRN-depleted cells following exposure to benzo[a]pyrene treatment. Benzo[a]pyrene-induced double strand breaks in RECQ1-depleted cells were dependent on DNA-PK activity. Notably, loss of WRN in RECQ1-depleted cells ameliorated benzo[a]pyrene toxicity. Collectively, our results provide first indication of non-redundant participation of WRN and RECQ1 in protection from the potentially carcinogenic effects of benzo[a]pyrene and hydroquinone.
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影响因子：
16.8
作者：
Berti, Matteo;Chaudhuri, Arnab Ray;Thangavel, Saravanabhavan;Gomathinayagam, Shivasankari;Kenig, Sasa;Vujanovic, Marko;Odreman, Federico;Glatter, Timo;Graziano, Simona;Mendoza-Maldonado, Ramiro;Marino, Francesca;Lucic, Bojana;Biasin, Valentina;Gstaiger, Matthias;Aebersold, Ruedi;Sidorova, Julia M.;Monnat, Raymond J., Jr.;Lopes, Massimo;Vindigni, Alessandro
通讯作者：
Vindigni, Alessandro
影响因子：
11.4
作者：
Ammazzalorso, Francesca;Pirzio, Livia Maria;Pichierri, Pietro
通讯作者：
Pichierri, Pietro
DOI：
10.1073/pnas.1216894110
发表时间：
2013-04-16
影响因子：
11.1
作者：
Izhar, Lior;Ziv, Omer;Livneh, Zvi
通讯作者：
Livneh, Zvi
对苯二酚诱导的 HepG2 细胞遗传毒性和氧化 DNA 损伤
影响因子：
5.1
作者：
Luo, Lihan;Jiang, Liping;Zhong, Laifu
通讯作者：
Zhong, Laifu
影响因子：
5.3
作者：
Kobayashi, Junya;Okui, Michiyo;Asaithamby, Aroumougame;Burma, Sandeep;Chen, Benjamin P. C.;Tanimoto, Keiji;Matsuura, Shinya;Komatsu, Kenshi;Chen, David J.
通讯作者：
Chen, David J.