Transcriptional activation of short interspersed elements by DNA‐damaging agents
Transcriptional activation of short interspersed elements by DNA‐damaging agents
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DNA 损伤剂对短散布元件的转录激活
DOI：
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
C. Thompson
中科院分区：
文献类型：
--
作者：
C. Rudin;C. Thompson
以人类Alu重复序列为代表的短散布元件（西内斯）是RNA聚合酶III（pol III）转录的序列，通过RNA中间体在基因组内复制。西内斯的复制在哺乳动物进化中广泛存在：估计5%的人类基因组由Alu重复序列组成。调控转录、逆转录和基因组DNA中SINE元件重新插入的机制知之甚少。在这里，我们报告说，表达的小鼠SINE转录的B1和B2类强烈上调后，长期暴露于顺铂，依托泊苷，或γ射线。在这些条件下，人类细胞中Alu转录物的类似诱导发生。这种诱导不是由于任一物种中pol III活性的普遍上调。含有外源性人Alu元件的鼠细胞的遗传毒性处理诱导Alu转录。伴随着西内斯表达的增加，在暴露于这些相同的DNA损伤剂后观察到细胞逆转录酶的增加。这些发现表明，基因组损伤可能是西内斯的重要激活剂，并且SINE迁移可能导致暴露于DNA损伤化疗后的继发性恶性肿瘤。© 2000 Wiley利斯公司
Short interspersed elements (SINEs), typified by the human Alu repeat, are RNA polymerase III (pol III)‐transcribed sequences that replicate within the genome through an RNA intermediate. Replication of SINEs has been extensive in mammalian evolution: an estimated 5% of the human genome consists of Alu repeats. The mechanisms regulating transcription, reverse transcription, and reinsertion of SINE elements in genomic DNA are poorly understood. Here we report that expression of murine SINE transcripts of both the B1 and B2 classes is strongly upregulated after prolonged exposure to cisplatin, etoposide, or gamma radiation. A similar induction of Alu transcripts in human cells occurs under these conditions. This induction is not due to a general upregulation of pol III activity in either species. Genotoxic treatment of murine cells containing an exogenous human Alu element induced Alu transcription. Concomitant with the increased expression of SINEs, an increase in cellular reverse transcriptase was observed after exposure to these same DNA‐damaging agents. These findings suggest that genomic damage may be an important activator of SINEs, and that SINE mobility may contribute to secondary malignancy after exposure to DNA‐damaging chemotherapy. © 2000 Wiley‐Liss, Inc.
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影响因子：
20.3
作者：
Broeker, PLS;Super, HG;Rowley, JD
通讯作者：
Rowley, JD
依托泊苷和顺铂联合化疗治疗晚期非小细胞肺癌后的急性非淋巴细胞白血病。
影响因子：
20.3
作者：
Ratain,MJ;Kaminer,LS;Bitran,JD;Larson,RA;LeBeau,MM;Skosey,C;Purl,S;Hoffman,PC;Wade,J;Vardiman,JW
通讯作者：
Vardiman,JW
影响因子：
14.9
作者：
LIU, WM;CHU, WM;SCHMID, CW
通讯作者：
SCHMID, CW
影响因子：
14.9
作者：
LIU, WM;MARAIA, RJ;SCHMID, CW
通讯作者：
SCHMID, CW
影响因子：
20.3
作者：
MINN, AJ;RUDIN, CM;THOMPSON, CB
通讯作者：
THOMPSON, CB