Wood R D
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, UK.
Biochimie. 1999 Jan-Feb;81(1-2):39-44. doi: 10.1016/s0300-9084(99)80036-4.
For the bulk of mammalian DNA, the core protein factors needed for damage recognition and incision during nucleotide excision repair (NER) are the XPA protein, the heterotrimeric RPA protein, the 6 to 9-subunit TFIIH, the XPC-hHR23B complex, the XPG nuclease, and the ERCC1-XPF nuclease. With varying efficiencies, NER can repair a very wide range of DNA adducts, from bulky helical distortions to subtle modifications on sugar residues. Several of the NER factors have an affinity for damaged DNA. The strongest binding factor appears to be XPC-hHR23B but preferential binding to damage is also a property of XPA, RPA, and components of TFIIH. It appears that in order to be repaired by NER, an adduct in DNA must have two features: it must create a helical distortion, and there must be a change in DNA chemistry. Initial recognition of the distortion is the most likely function for XPC-hHR23B and perhaps XPA and RPA, whereas TFIIH is well-suited to locate the damaged DNA strand by locating altered DNA chemistry that blocks translocation of the XPB and XPD components.
对于大多数哺乳动物DNA而言，核苷酸切除修复（NER）过程中损伤识别和切割所需的核心蛋白因子包括XPA蛋白、异源三聚体RPA蛋白、6至9个亚基的TFIIH、XPC-hHR23B复合物、XPG核酸酶以及ERCC1-XPF核酸酶。NER能够以不同效率修复范围极为广泛的DNA加合物，从严重的螺旋结构扭曲到糖残基上的细微修饰。几种NER因子对受损DNA具有亲和力。结合能力最强的因子似乎是XPC-hHR23B，但XPA、RPA以及TFIIH的组分也具有优先结合损伤部位的特性。看来，DNA中的加合物若要通过NER进行修复，必须具备两个特征：它必须造成螺旋结构扭曲，并且DNA化学性质必须发生改变。对这种扭曲的初始识别最有可能是XPC-hHR23B以及或许还有XPA和RPA的功能，而TFIIH非常适合通过定位阻碍XPB和XPD组分易位的改变的DNA化学性质来确定受损的DNA链。
