Rpb1 sumoylation in response to UV radiation or transcriptional impairment in yeast.
Rpb1 sumoylation in response to UV radiation or transcriptional impairment in yeast.
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DOI：
10.1371/journal.pone.0005267
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Chen X;Ding B;LeJeune D;Ruggiero C;Li S
泛素和小泛素样调节剂（SUMO）对蛋白质的共价修饰已经被揭示参与了大量的细胞过程，包括转录、DNA修复和DNA损伤反应。众所周知，在哺乳动物和酵母细胞中，RNA聚合酶II（Pol II）的最大亚基Rpb 1响应于阻断转录延伸的DNA损伤而被泛素化并随后降解。然而，关于Pol II如何响应受损的DNA并为DNA损伤相关的细胞过程传递信号仍然是一个谜。我们发现，Rpb 1也sumoylated在酵母细胞UV辐射或损伤的转录延伸，这种修改是独立的DNA损伤检查点激活。Ubc 9是一种E2 SUMO结合酶，Siz 1是一种E3 SUMO连接酶，在Rpb 1类小泛素化中起重要作用。K1487位于Rpb 1的C-末端结构域和球状结构域之间的酸性连接区，是主要的sumoylation位点。rpb 1类泛素化不受其泛素化的影响，反之亦然，表明这两个过程不串扰。在K1487处取消Rpb 1类小泛素化不影响UV诱导的DNA损伤的转录延伸或转录偶联修复（TCR）。然而，TCR的缺陷增强了UV诱导的Rpb 1类小泛素化，这可能是由于在基因的转录链中持续存在转录阻断DNA损伤。值得注意的是，废除Rpb 1 SUMO化K1487导致增强和延长紫外线诱导的磷酸化Rad 53，特别是在TCR缺陷的细胞，这表明SUMO化在抑制DNA损伤检查点反应中发挥作用引起的转录阻断病变。我们的研究结果表明，一种新的共价修饰的RPB 1在响应UV诱导的DNA损伤或转录损伤，并解开一个重要的联系之间的修改和DNA损伤检查点响应。
Covalent modifications of proteins by ubiquitin and the Small Ubiquitin-like MOdifier (SUMO) have been revealed to be involved in a plethora of cellular processes, including transcription, DNA repair and DNA damage responses. It has been well known that in response to DNA damage that blocks transcription elongation, Rpb1, the largest subunit of RNA polymerase II (Pol II), is ubiquitylated and subsequently degraded in mammalian and yeast cells. However, it is still an enigma regarding how Pol II responds to damaged DNA and conveys signal(s) for DNA damage-related cellular processes. We found that Rpb1 is also sumoylated in yeast cells upon UV radiation or impairment of transcription elongation, and this modification is independent of DNA damage checkpoint activation. Ubc9, an E2 SUMO conjugase, and Siz1, an E3 SUMO ligase, play important roles in Rpb1 sumoylation. K1487, which is located in the acidic linker region between the C-terminal domain and the globular domain of Rpb1, is the major sumoylation site. Rpb1 sumoylation is not affected by its ubiquitylation, and vice versa, indicating that the two processes do not crosstalk. Abolishment of Rpb1 sumoylation at K1487 does not affect transcription elongation or transcription coupled repair (TCR) of UV-induced DNA damage. However, deficiency in TCR enhances UV-induced Rpb1 sumoylation, presumably due to the persistence of transcription-blocking DNA lesions in the transcribed strand of a gene. Remarkably, abolishment of Rpb1 sumoylation at K1487 causes enhanced and prolonged UV-induced phosphorylation of Rad53, especially in TCR-deficient cells, suggesting that the sumoylation plays a role in restraining the DNA damage checkpoint response caused by transcription-blocking lesions. Our results demonstrate a novel covalent modification of Rpb1 in response to UV induced DNA damage or transcriptional impairment, and unravel an important link between the modification and the DNA damage checkpoint response.
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影响因子：
16
作者：
Anindya, Roy;Ayguen, Ozan;Svejstrup, Jesper Q.
通讯作者：
Svejstrup, Jesper Q.
影响因子：
64.5
作者：
Johnson, ES;Gupta, AA
通讯作者：
Gupta, AA
DOI：
10.1073/pnas.0705317104
发表时间：
2007-07-31
影响因子：
11.1
作者：
Derheimer, Frederick A.;O'Hagan, Heather M.;Ljungman, Mats
通讯作者：
Ljungman, Mats
影响因子：
5.3
作者：
Jiang, GC;Sancar, A
通讯作者：
Sancar, A
影响因子：
11.4
作者：
Jansen, LET;den Dulk, H;Brouwer, J
通讯作者：
Brouwer, J