title: Transcription inhibition by DRB potentiates recombinational repair of UV lesions in mammalian cells.
abstract: Homologous recombination (HR) is intricately associated with replication, transcription and DNA repair in all organisms studied. However, the interplay between all these processes occurring simultaneously on the same DNA molecule is still poorly understood. Here, we study the interplay between transcription and HR during ultraviolet light (UV)-induced DNA damage in mammalian cells. Our results show that inhibition of transcription with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) increases the number of UV-induced DNA lesions (γH2AX, 53BP1 foci formation), which correlates with a decrease in the survival of wild type or nucleotide excision repair defective cells. Furthermore, we observe an increase in RAD51 foci formation, suggesting HR is triggered in response to an increase in UV-induced DSBs, while inhibiting transcription. Unexpectedly, we observe that DRB fails to sensitise HR defective cells to UV treatment. Thus, increased RAD51 foci formation correlates with increased cell death, suggesting the existence of a futile HR repair of UV-induced DSBs which is linked to transcription inhibition.
authors.affiliation: Department of Genetics, Microbiology, and Toxicology, Stockholm University, Stockholm, Sweden.
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Stoimenov
authors.forename: Niklas
authors.initials: N
authors.lastname: Schultz
authors.forename: Ponnari
authors.initials: P
authors.lastname: Gottipati
authors.forename: Thomas
authors.initials: T
authors.lastname: Helleday
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D011995:Recombination, Genetic / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D004004:Dichlororibofuranosylbenzimidazole