Torres-Ramos C A, Johnson R E, Prakash L, Prakash S
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061, USA.
Mol Cell Biol. 2000 May;20(10):3522-8. doi: 10.1128/MCB.20.10.3522-3528.2000.
In eukaryotes, DNA damage induced by ultraviolet light and other agents which distort the helix is removed by nucleotide excision repair (NER) in a fragment approximately 25 to 30 nucleotides long. In humans, a deficiency in NER causes xeroderma pigmentosum (XP), characterized by extreme sensitivity to sunlight and a high incidence of skin cancers. Abasic (AP) sites are formed in DNA as a result of spontaneous base loss and from the action of DNA glycosylases involved in base excision repair. In Saccharomyces cerevisiae, AP sites are removed via the action of two class II AP endonucleases, Apn1 and Apn2. Here, we provide evidence for the involvement of NER in the removal of AP sites and show that NER competes with Apn1 and Apn2 in this repair process. Inactivation of NER in the apn1Delta or apn1Delta apn2Delta strain enhances sensitivity to the monofunctional alkylating agent methyl methanesulfonate and leads to further impairment in the cellular ability to remove AP sites. A deficiency in the repair of AP sites may contribute to the internal cancers and progressive neurodegeneration that occur in XP patients.
在真核生物中，由紫外线及其他使螺旋结构扭曲的因素诱导产生的DNA损伤，通过核苷酸切除修复（NER）被去除，切除的片段长度约为25至30个核苷酸。在人类中，NER功能缺陷会导致着色性干皮病（XP），其特征为对阳光极度敏感且皮肤癌发病率很高。无碱基（AP）位点在DNA中由于自发碱基丢失以及参与碱基切除修复的DNA糖基化酶的作用而形成。在酿酒酵母中，AP位点通过两种II类AP内切核酸酶Apn1和Apn2的作用被去除。在此，我们提供了NER参与去除AP位点的证据，并表明在这个修复过程中NER与Apn1和Apn2存在竞争。在apn1Delta或apn1Delta apn2Delta菌株中NER失活会增强对单功能烷化剂甲磺酸甲酯的敏感性，并导致细胞去除AP位点的能力进一步受损。AP位点修复缺陷可能导致XP患者发生内部癌症和进行性神经退行性变。
