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首页> 外文期刊>Cell cycle >Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage.
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Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage.

机译：哺乳动物SWI / SNF染色质重塑复合体在细胞对UV损伤的反应中的作用。

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Mammalian cells exhibit complex cellular responses to DNA damage, including cell cycle arrest, DNA repair and apoptosis. Defects in any one of these responses can result in carcinogenesis. Absence of the chromatin remodeling complex Swi/Snf is found in many instances of cancer, and we have investigated its role in the UV damage response. The human carcinoma cell line SW13 is deficient in Swi/Snf and is very sensitive to UV radiation. In contrast, SW13 cells with ectopic Brg1 expression regain active Swi/Snf and become significantly more resistant to UV radiation. Sensitivity to UV light correlates well with dramatic UV induced apoptosis in SW13 cells, but not in SW13 cells expressing Brg1. We show that SW13 cells synchronized at the G(1)/S border progress into S phase after UV irradiation, and this checkpoint deficiency is corrected after Brg1 expression is restored. Interestingly, Brg1 expression in SW13 cells restores expression of two DNA damage responsive genes, Gadd45a and p21. Furthermore, Gadd45a induction and p21 degradation were observed in the Brg1-expressing SW13 cells after UV irradiation. Our findings demonstrate that Swi/Snf protects cells against deleterious consequences of UV induced DNA damage. These results also indicate that Swi/Snf may modulate checkpoint activation after UV damage via regulation of the two PCNA-binding proteins Gadd45a and p21.
机译：哺乳动物细胞对DNA损伤表现出复杂的细胞反应，包括细胞周期停滞，DNA修复和细胞凋亡。这些反应中任何一种的缺陷都可能导致癌变。在许多癌症病例中都没有发现染色质重塑复合物Swi / Snf，我们已经研究了其在紫外线损伤反应中的作用。人癌细胞系SW13缺乏Swi / Snf，并且对紫外线辐射非常敏感。相反，具有异位Brg1表达的SW13细胞会恢复活性Swi / Snf，并且对紫外线的抵抗力明显增强。对紫外光的敏感性与SW13细胞中剧烈的UV诱导的细胞凋亡相关，而在表达Brg1的SW13细胞中却没有。我们显示在紫外线照射后，在G（1）/ S边界同步的SW13细胞进入S期，并且在恢复Brg1表达后纠正了这个检查点缺陷。有趣的是，SW13细胞中的Brg1表达恢复了两个DNA损伤反应基因Gadd45a和p21的表达。此外，在紫外线照射后，在表达Brg1的SW13细胞中观察到Gadd45a诱导和p21降解。我们的发现表明Swi / Snf保护细胞免受UV诱导的DNA损伤的有害影响。这些结果还表明，Swi / Snf可能通过调节两个PCNA结合蛋白Gadd45a和p21来调节紫外线损伤后的检查点激活。

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