Transcription-coupled repair: a multifunctional signaling pathway.
Transcription-coupled repair: a multifunctional signaling pathway.
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转录偶联修复：多功能信号通路。
DOI：
10.1101/sqb.2000.65.561
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Leadon,SA
中科院分区：
文献类型：
--
作者：
Leadon,SA
CS是一种罕见的隐性遗传模式的阳光敏感性疾病。其特征在于严重的生长缺陷伴恶病质、神经元脱髓鞘、智力迟钝、小头畸形、骨骼和视网膜异常以及龋齿，但无癌症倾向。已经报道了超过140例CS病例，并且来自受影响个体的细胞定义了五个互补组。大多数患者仅表现出CS症状，属于A组和B组（CSA和CS B）。CSA基因编码属于WD-重复家族的蛋白质（Henning等，1995），其成员调节多种细胞功能，包括细胞分裂、信号转导、mRNA修饰和转录。CSB基因的产物（Troelstra等，1992）含有一个具有扩展和多样SNF 2蛋白家族特征的多个ATP酶/推定解旋酶基序的区域。CS缺陷的基因产物是UV和电离辐射诱导的DNA的TCR所必需的（Venema等，1990; Leadon和库珀1993）。由于CSB编码一种推定的解旋酶（Troelstra et al. 1992），其产物可解开DNA，从而从DNA中置换停滞的RNA聚合酶复合物，使修复蛋白进入病变。CSA基因产物也可能作为一种一般介质，将修复蛋白募集到受损部位。由于迄今为止研究的CS组A和B突变体的唯一代表同样缺乏将UV损伤的修复靶向活性基因的能力（Venema et al. 1990; Leadon and库珀1993），因此在哺乳动物细胞中，该过程中对两种基因产物的需求似乎是绝对的。然而，CSA突变细胞系在电离辐射损伤的优先修复中仅部分缺陷的发现提供了两种基因产物可分离作用的第一个证据（Leadon和库珀1993）。在非常罕见的情况下，互补分析将一些CS患者分配到着色性干皮病（XP）组B、D或G;这些XP/CS患者中的一些也呈现XP表型。XPB（Weeda et al.
CS is a rare sun-sensitivity disorder with a recessive inheritance pattern. It is characterized by severe growth defects with cachexia, neuronal demyelination, mental retardation, microcephaly, skeletal and retinal abnormalities, and dental caries, but no cancer predisposition. More than 140 CS cases have been reported, and cells from affected individuals define five complementation groups. Most patients exhibit only CS symptoms and belong to groups A and B (CSA and CSB). The CSA gene codes for a protein belonging to the WD-repeat family (Henning et al. 1995), whose members regulate diverse cellular functions, including cell division, signal transduction, mRNA modification, and transcription. The product of the CSB gene (Troelstra et al. 1992) contains a region of multiple ATP-ase/putative helicase motifs characteristic of the expanding and diverse SNF2 protein family. Members of this family can have roles in chromatin remodeling or maintenance, activation or repression of transcription, and DNA recombination or repair.The gene products defective in CS are required for the TCR of both UV-and ionizing-radiation-induced DNA (Venema et al. 1990; Leadon and Cooper 1993). Since CSB encodes a putative helicase (Troelstra et al. 1992), its product may unwind DNA and thus displace a stalled RNA polymerase complex from the DNA, allowing repair proteins access to the lesion. It is also possible that the CSA gene product acts as a general mediator that recruits repair proteins to the damaged site. Since the sole representatives of CS group A and B mutants studied so far are equally devoid of the ability to target repair of UV damage to active genes (Venema et al. 1990; Leadon and Cooper 1993), the requirement for both gene products in this process appears to be absolute in mammalian cells. However, the finding that the CSA mutant cell line is only partially defective in preferential repair of ionizing radiation damage provides the first evidence of separable roles for the two gene products (Leadon and Cooper 1993). In very rare cases, complementation analyses have assigned some CS patients to xeroderma pigmentosum (XP) groups B, D, or G; some of these XP/CS patients also present an XP phenotype. The XPB (Weeda et al.