Focal Sites of DNA Repair Synthesis in Human Chromosomes

Nucleotide excision repair (NER) is the principle pathway by which the human cells eliminate UV-induced lesions from their genomic DNA, The process can be visualized through the labelling of the nucleotides that are incoporated into repair patches, following the excision of the damaged stretch of DNA. In this study we have visualized sites of DNA repair synthesis (DRS) in human interphase and metaphase chromosomes after very short times (2.5-30 min) of postirradiation labelling in vivo with 5-iododeoxyuridine. A limited number (<50 per nucleus) of discrete nuclear DRS sites were seen in cells fixed immediately after labelling and the sites are also detectable in interphase and metaphase chromosomes visualized 48h after irradiation (3 J/m(2)). These observations strongly support the view that within a given short time window distinct chromosome domains are under extensive repair while in many other domains NER is slow. They argue against the general distributative NER process but are consistent with a processive scanning Of damaged domains. (C) 1999 Academic Press.