Falik-Zaccai Tzipora C, Keren Zohar, Slor Hanoch
Institute of Human Genetics, Western Galilee Hospital, Naharia, Israel.
Pediatr Endocrinol Rev. 2009 Dec;7(2):37-42.
Two of DNA's worst enemies, ultraviolet light and chemical carcinogens, can cause damage to the molecule by mutating individual nucleotides or changing its physical structure. In most cases, genomic integrity is restored by specialized suites of proteins dedicated to repairing specific types of injuries. One restoration mechanism, called nucleotide excision repair (NER), recruits and coordinates the services of 20-30 proteins to recognize and remove structure-impairing lesions, including those induced by ultraviolet (UV) light. Mutations in a gene that encodes a protein from the NER machinery might cause a wide variety of rare inherited human disorders. Sun sensitivity, cancer, developmental retardation, neurodegeneration and premature aging characterize these syndromes. Identification of the causative genes and proteins in affected families in Israel allowed us to establish accurate molecular diagnosis of couples at risk, and provide them with better genetic counseling.
DNA的两个最可怕的敌人，紫外线和化学致癌物，会通过使单个核苷酸发生突变或改变其物理结构来对该分子造成损害。在大多数情况下，基因组完整性会通过专门用于修复特定类型损伤的蛋白质组来恢复。一种称为核苷酸切除修复（NER）的修复机制会招募并协调20 - 30种蛋白质的作用，以识别和去除损害结构的损伤，包括由紫外线（UV）诱导的损伤。编码NER机制中一种蛋白质的基因突变可能会导致多种罕见的人类遗传性疾病。对阳光敏感、患癌症、发育迟缓、神经退行性变和早衰是这些综合征的特征。对以色列受影响家庭中致病基因和蛋白质的鉴定，使我们能够对有风险的夫妇进行准确的分子诊断，并为他们提供更好的遗传咨询。
