Liakos Anastasios, Lavigne Matthieu D, Fousteri Maria
Biomedical Sciences Research Center 'Alexander Fleming', 34 Fleming st., 16672, Vari, Athens, Greece.
Adv Exp Med Biol. 2017;1007:17-39. doi: 10.1007/978-3-319-60733-7_2.
DNA damage poses a constant threat to genome integrity taking a variety of shapes and arising by normal cellular metabolism or environmental insults. Human syndromes, characterized by increased cancer pre-disposition or early onset of age-related pathology and developmental abnormalities, often result from defective DNA damage responses and compromised genome integrity. Over the last decades intensive research worldwide has made important contributions to our understanding of the molecular mechanisms underlying genomic instability and has substantiated the importance of DNA repair in cancer prevention in the general population. In this chapter, we discuss Nucleotide Excision Repair pathway, the causative role of its components in disease-related pathology and recent technological achievements that decipher mutational landscapes and may facilitate pathological classification and personalized therapy.
DNA损伤对基因组完整性构成持续威胁，其形式多样，可由正常细胞代谢或环境损伤引发。以癌症易感性增加、与年龄相关的病理状况早期出现以及发育异常为特征的人类综合征，往往源于DNA损伤反应缺陷和基因组完整性受损。在过去几十年里，全球范围内的深入研究为我们理解基因组不稳定背后的分子机制做出了重要贡献，并证实了DNA修复在普通人群癌症预防中的重要性。在本章中，我们将讨论核苷酸切除修复途径、其组成部分在疾病相关病理中的致病作用，以及最近的技术成果，这些成果能够解读突变图谱，并可能有助于病理分类和个性化治疗。
