Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
J Biol Chem. 2020 Dec 11;295(50):17374-17380. doi: 10.1074/jbc.AC120.016325. Epub 2020 Oct 21.
In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11-13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24-32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of We find that , which possesses homologs of the , , and genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to .
在核苷酸切除修复中,通过在损伤处两侧协同进行双切口,切除基因组中的大体积 DNA 损伤,如紫外线诱导的环丁烷嘧啶二聚体,然后进行缺口填充和连接。到目前为止,已经发现了两种双切口模式:原核型,切除 11-13 个核苷酸长的寡聚物中的损伤;真核型,切除 24-32 个核苷酸长的寡聚物中的损伤。然而,最近的一项研究报道称,UvrC 蛋白在源自损伤处 3' 端 15 个核苷酸和 5' 端 9 个核苷酸侧翼的 25 个核苷酸寡核苷酸中以类似于酵母和人类的方式去除损伤。为了验证该模型,我们使用 切除测定法和我们实验室开发的全基因组修复图谱方法,确定了 的修复模式和全基因组修复图谱。我们发现,具有 、 和 基因同源物的 以与原核模式相同的方式从基因组中切除环丁烷嘧啶二聚体,通过在光产物的 5' 端切割 7 个核苷酸和 3 或 4 个核苷酸,以及以类似于 的方式进行转录偶联修复。