SUV39H1 downregulation induces deheterochromatinization of satellite regions and senescence after exposure to ionizing radiation.
SUV39H1 downregulation induces deheterochromatinization of satellite regions and senescence after exposure to ionizing radiation.
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DOI：
10.3389/fgene.2014.00411
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发表时间：
2014
影响因子：
3.7
通讯作者：
Kovalchuk O
中科院分区：
文献类型：
--
作者：
Sidler C;Li D;Wang B;Kovalchuk I;Kovalchuk O
虽然大多数癌症患者在诊断和治疗过程中暴露在电离辐射中，但辐射敏感性的年龄差异尚未得到很好的了解。放射敏感性的特征是放射治疗出现副作用，如继发性恶性肿瘤、发育缺陷和免疫功能受损。然而，对触发这些副作用的分子机制的了解还不完整。在这里，我们使用了一个体外系统，并显示了低衰老的正常人二倍体成纤维细胞(WI-38)对5GyIR的反应而衰老，而高度衰老的培养细胞没有表现出细胞周期调节的变化，衰老细胞的百分比仅略有增加。我们的研究表明，这与负责细胞周期进程、细胞凋亡、DNA修复和衰老的基因以及转录和表观遗传调节因子的表达变化有关。此外，我们提出了SUV39H1表达的下调以及H3K9me3水平的相应降低在IR诱导衰老中的作用。
While the majority of cancer patients are exposed to ionizing radiation during diagnostic and therapeutic procedures, age-dependent differences in radiation sensitivity are not yet well understood. Radiation sensitivity is characterized by the appearance of side effects to radiation therapy, such as secondary malignancies, developmental deficits, and compromised immune function. However, the knowledge of the molecular mechanisms that trigger these side effects is incomplete. Here we used an in vitro system and showed that low-senescent normal human diploid fibroblasts (WI-38) senesce in response to 5 Gy IR, while highly senescent cultures do not show changes in cell cycle regulation and only a slight increase in the percentage of senescent cells. Our study shows that this is associated with changes in the expression of genes responsible for cell cycle progression, apoptosis, DNA repair, and aging, as well as transcriptional and epigenetic regulators. Furthermore, we propose a role of the downregulation of SUV39H1 expression, a histone methyltransferase that specifically trimethylates H3K9, and the corresponding reduction in H3K9me3 levels in the establishment of IR-induced senescence.
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影响因子：
8
作者：
Cherrier, T.;Suzanne, S.;Redel, L.;Calao, M.;Marban, C.;Samah, B.;Mukerjee, R.;Schwartz, C.;Gras, G.;Sawaya, B. E.;Zeichner, S. L.;Aunis, D.;Van Lint, C.;Rohr, O.
通讯作者：
Rohr, O.
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
8
作者：
Kaneko, Y;Watanabe, N;Nakanishi, M
通讯作者：
Nakanishi, M
影响因子：
5.7
作者：
Joosten, Andreas;Matzinger, Oscar;Moeckli, Raphael
通讯作者：
Moeckli, Raphael
影响因子：
9.2
作者：
Lehnertz, B;Ueda, Y;Peters, AHFM
通讯作者：
Peters, AHFM