Molecular characterization of an acidic region deletion mutant of Cockayne syndrome group B protein.
Molecular characterization of an acidic region deletion mutant of Cockayne syndrome group B protein.
复制标题
科凯恩综合征 B 组蛋白酸性区域缺失突变体的分子特征。
DOI：
10.1093/nar/28.16.3151
复制
发表时间：
2000
影响因子：
14.9
通讯作者：
V. Bohr
中科院分区：
文献类型：
--
作者：
M. Sunesen;R. Selzer;R. Brosh;A. Balajee;T. Stevnsner;V. Bohr
柯凯因综合征（CS）是一种以出生后生长衰竭、神经系统异常和过早衰老为特征的人类遗传性疾病。CS细胞表现出对紫外光的高敏感性，紫外线照射后RNA合成恢复延迟和转录偶联修复缺陷（TCR）。鉴定出了CS的两个遗传互补群，分别为CS- a和CS- b。CSB基因编码解旋酶结构域和解旋酶结构域的高酸性区域n端。本研究描述了一个编码酸性区域完全缺失的CSB突变等位基因的遗传特征。我们测试了其补充人类CS-B细胞的仓鼠同源物UV61对紫外线和基因毒性剂n -乙酰氧基-2-乙酰氨基芴（NA-AAF）敏感性的能力。删除39个连续的氨基酸，其中约60%带负电荷，并不影响蛋白质对UV或NA-AAF敏感表型的补充能力。我们的数据表明，CSB的高酸性区域对于紫外线和na - aaf诱导的DNA损伤的TCR和一般基因组修复途径不是必需的。
Cockayne syndrome (CS) is a human genetic disorder characterized by post-natal growth failure, neurological abnormalities and premature aging. CS cells exhibit high sensitivity to UV light, delayed RNA synthesis recovery after UV irradiation and defective transcription-coupled repair (TCR). Two genetic complementation groups of CS have been identified, designated CS-A and CS-B. The CSB gene encodes a helicase domain and a highly acidic region N-terminal to the helicase domain. This study describes the genetic characterization of a CSB mutant allele encoding a full deletion of the acidic region. We have tested its ability to complement the sensitivity of UV61, the hamster homolog of human CS-B cells, to UV and the genotoxic agent N-acetoxy-2-acetylaminofluorene (NA-AAF). Deleting 39 consecutive amino acids, of which approximately 60% are negatively charged, did not impact on the ability of the protein to complement the sensitive phenotype of UV61 cells to either UV or NA-AAF. Our data indicate that the highly acidic region of CSB is not essential for the TCR and general genome repair pathways of UV- and NA-AAF-induced DNA lesions.