Focal sites of DNA repair synthesis in human chromosomes

Nucleotide excision repair (NER) is the principle pathway by which the huma n cells eliminate UV-induced lesions from their genomic DNA, The process ca n be visualized through the labelling of the nucleotides that are incoporat ed into repair patches, following the excision of the damaged stretch of DN A. 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 m in) 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 inte rphase and metaphase chromosomes visualized 48h after irradiation (3 J/m(2) ). These observations strongly support the view that within a given short t ime window distinct chromosome domains are under extensive repair while in many other domains NER is slow. They argue against the general distributati ve NER process but are consistent with a processive scanning Of damaged dom ains. (C) 1999 Academic Press.