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哺乳动物细胞中自发的和紫外线诱导的直接重复序列重组常常导致重复序列缺失。

Spontaneous and ultraviolet light-induced direct repeat recombination in mammalian cells frequently results in repeat deletion.

作者信息

Bill C A, Nickoloff J A

机构信息

Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, Albuquerque, NM 87131, USA.

出版信息

Mutat Res. 2001 Nov 1;487(1-2):41-50. doi: 10.1016/s0921-8777(01)00101-x.

DOI:10.1016/s0921-8777(01)00101-x
PMID:11595407
Abstract

Recombination is enhanced by transcription and by DNA damage caused by ultraviolet light (UV). Recombination between direct repeats can occur by gene conversion without an associated crossover, which maintains the gross repeat structure. There are several possible mechanisms that delete one repeat and the intervening sequences (gene conversion associated with a crossover, unequal sister chromatid exchange, and single-strand annealing). We examined transcription-enhanced spontaneous recombination, and UV-induced recombination between neomycin (neo) direct repeats. One neo gene was driven by the inducible MMTV promoter. Multiple (silent) markers in the second neo gene were used to map conversion tracts. These markers are thought to inhibit spontaneous recombination, and our data suggest that this inhibition is partially overcome by high level transcription. Recombination was stimulated by transcription and by UV doses of 6-12J/m(2), but not by 18J/m(2). About 70% of spontaneous and UV-induced products were deletions. In contrast, only 3% of DSB-induced products were deletions. We propose that these product spectra differ because spontaneous and UV-induced recombination is replication-dependent, whereas DSB-induced recombination is replication-independent.

摘要

转录以及紫外线(UV)造成的DNA损伤会增强重组。同向重复序列之间的重组可通过基因转换发生,而不伴有相关的交叉,这维持了重复序列的总体结构。存在几种可能的机制可删除一个重复序列及中间序列(与交叉相关的基因转换、不等姐妹染色单体交换和单链退火)。我们研究了转录增强的自发重组以及紫外线诱导的新霉素(neo)同向重复序列之间的重组。一个neo基因由可诱导的MMTV启动子驱动。第二个neo基因中的多个(沉默)标记用于绘制转换片段。这些标记被认为可抑制自发重组,我们的数据表明这种抑制可被高水平转录部分克服。转录以及6 - 12J/m(2)的紫外线剂量可刺激重组,但18J/m(2)的剂量则不能。约70%的自发和紫外线诱导产物为缺失型。相比之下,双链断裂(DSB)诱导产物中只有3%为缺失型。我们认为这些产物谱不同是因为自发和紫外线诱导的重组依赖复制,而DSB诱导的重组不依赖复制。

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1
Spontaneous and ultraviolet light-induced direct repeat recombination in mammalian cells frequently results in repeat deletion.哺乳动物细胞中自发的和紫外线诱导的直接重复序列重组常常导致重复序列缺失。
Mutat Res. 2001 Nov 1;487(1-2):41-50. doi: 10.1016/s0921-8777(01)00101-x.
2
Gene conversion and deletion frequencies during double-strand break repair in human cells are controlled by the distance between direct repeats.人类细胞双链断裂修复过程中的基因转换和缺失频率受同向重复序列之间距离的控制。
Nucleic Acids Res. 2005 Mar 14;33(5):1574-80. doi: 10.1093/nar/gki295. Print 2005.
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Preferential repair of UV damage in highly transcribed DNA diminishes UV-induced intrachromosomal recombination in mammalian cells.高度转录的DNA中紫外线损伤的优先修复减少了哺乳动物细胞中紫外线诱导的染色体内重组。
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Chromosomal double-strand breaks induce gene conversion at high frequency in mammalian cells.染色体双链断裂在哺乳动物细胞中高频诱导基因转换。
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Extrachromosomal unequal homologous recombination and gene conversion in simian kidney cells: effects of UV damage.
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BRCA1 regulates RAD51 function in response to DNA damage and suppresses spontaneous sister chromatid replication slippage: implications for sister chromatid cohesion, genome stability, and carcinogenesis.BRCA1在DNA损伤应答中调节RAD51功能,并抑制自发的姐妹染色单体复制滑移:对姐妹染色单体黏连、基因组稳定性和致癌作用的影响。
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Transcriptional effects on double-strand break-induced gene conversion tracts.对双链断裂诱导的基因转换区段的转录影响。
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Inactivation of the RAD51 recombination pathway stimulates UV-induced mutagenesis in mammalian cells.RAD51重组途径的失活会刺激哺乳动物细胞中紫外线诱导的诱变。
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An xrcc4 defect or Wortmannin stimulates homologous recombination specifically induced by double-strand breaks in mammalian cells.Xrcc4缺陷或渥曼青霉素可刺激哺乳动物细胞中由双链断裂特异性诱导的同源重组。
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Sister chromatid gene conversion is a prominent double-strand break repair pathway in mammalian cells.姐妹染色单体基因转换是哺乳动物细胞中一种重要的双链断裂修复途径。
EMBO J. 2000 Jul 3;19(13):3398-407. doi: 10.1093/emboj/19.13.3398.

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