title: Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin.
abstract: During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression.
authors.affiliation: Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. junkom@med.tohoku.ac.jp
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Komura
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ikehata
authors.forename: Toshio
authors.initials: T
authors.lastname: Mori
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
mesh_terms: D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D015894:Genome, Human; D006801:Humans; D008938:Mitosis / Q000528:radiation effects; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011740:Pyrimidine Dimers; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D014965:X-Rays
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D011740:Pyrimidine Dimers; C058406:pyrimidine-pyrimidone dimer; D013762:Tetrahydrofolate Dehydrogenase