title: Nucleotide excision repair in Trypanosoma brucei: specialization of transcription-coupled repair due to multigenic transcription.
abstract: Nucleotide excision repair (NER) is a highly conserved genome repair pathway acting on helix distorting DNA lesions. NER is divided into two subpathways: global genome NER (GG-NER), which is responsible for repair throughout genomes, and transcription-coupled NER (TC-NER), which acts on lesions that impede transcription. The extent of the Trypanosoma brucei genome that is transcribed is highly unusual, since most genes are organized in multigene transcription units, each transcribed from a single promoter. Given this transcription organization, we have addressed the importance of NER to T. brucei genome maintenance by performing RNAi against all predicted contributing factors. Our results indicate that TC-NER is the main pathway of NER repair, but only CSB, XPBz and XPG contribute. Moreover, we show that UV lesions are inefficiently repaired in T. brucei, perhaps due to preferential use of RNA polymerase translesion synthesis. RNAi of XPC and DDB was found to be lethal, and we show that these factors act in inter-strand cross-link repair. XPD and XPB appear only to act in transcription, not repair. This work indicates that the predominance of multigenic transcription in T. brucei has resulted in pronounced adaptation of NER relative to the host and may be an attractive drug target.
authors.affiliation: Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Caixa Postal 486, Belo Horizonte, 30161-970, MG, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Machado
authors.forename: João P
authors.initials: JP
authors.lastname: Vieira-da-Rocha
authors.forename: Isabela Cecilia
authors.initials: IC
authors.lastname: Mendes
authors.forename: Matheus A
authors.initials: MA
authors.lastname: Rajão
authors.forename: Lucio
authors.initials: L
authors.lastname: Marcello
authors.forename: Mainá
authors.initials: M
authors.lastname: Bitar
authors.forename: Marcela G
authors.initials: MG
authors.lastname: Drummond
authors.forename: Priscila
authors.initials: P
authors.lastname: Grynberg
authors.forename: Denise A A
authors.initials: DA
authors.lastname: Oliveira
authors.forename: Catarina
authors.initials: C
authors.lastname: Marques
authors.forename: Ben
authors.initials: B
authors.lastname: Van Houten
authors.forename: Richard
authors.initials: R
authors.lastname: McCulloch
mesh_terms: D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D020043:Genes, Essential; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D045643:DNA Repair Enzymes