REPAIR OF BIPYRIMIDINE PHOTOPRODUCTS AT TELOMERES OF ULTRAVIOLET LIGHT IRRADIATED MAMMALIAN CELLS

摘要: Telomeres at chromosome ends promote genome stability, survival, and proliferation in cells, prevent degenerative diseases cancer humans. Human telomeres are 10-15 kilobases long consist of about 1500 tandem TTAGGG repeats. Six telomeric proteins form a shelterin complex that protects the from being recognized as break, thereby preventing inappropriate repair fusions. Telomeric DNA sequences vulnerable to ultraviolet light (UV)-induced damage. UV creates primarily two types photoproducts within DNA: cyclobutane pyrimidine dimers (CPDs) 6-4 (6-4 PPs). Unrepaired can stall or block replication transcription, if tolerated bypassed, introduce mutations cause genomic instability which drive carcinogenesis. In DNA, these potentially harmful cellular effects avoided through specialized nucleotide excision (NER) pathway removes restores normal DNA. This dissertation investigated also they repaired over time by NER. We exposed skin fibroblasts BJ-hTERT (NER proficient) XP-A deficient) 10 J/m2 UVC induces CPD PP lesions. then extracted measured rate lesion disappearance. Post exposure, cells all detectable PPs six hours CPDs days. However, did not PPs. observed unrepaired inhibit telomere TRF1 protein binding vitro, irradiation NER deficient causes aberrations. Our novel findings have uncovered presence importance major increase our understanding how bulky adducts may impact structure function. Telomere maintenance is essential protection against age-related The public health relevance study thus, relates its potential usefulness developing biomarkers toxicology for aging cancer.