Trypanosoma brucei harbors a divergent XPB helicase paralog that is specialized in nucleotide excision repair and conserved among kinetoplastid organisms

• Published in: Molecular microbiology Vol. 90; no. 6
• Main Authors: Badjatia, Nitika, Nguyen, Tu N, Lee, Ju Huck, Günzl, Arthur
• Format: Journal Article
• Language: English
• Published: 08.11.2013
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.12435

Conserved from yeast to humans, TFIIH is essential for RNA polymerase II transcription and nucleotide excision repair (NER). TFIIH consists of a core that includes the DNA helicase Xeroderma pigmentosum B (XPB) and a kinase subcomplex. Trypanosoma brucei TFIIH harbors all core complex components and is indispensable for RNA polymerase II transcription of spliced leader RNA genes ( SLRNAs ). Kinetoplastid organisms, however, possess two highly divergent XPB paralogs with only the larger being identified as a TFIIH subunit in T. brucei . Here we show that a knockout of the gene for the smaller paralog, termed XPB-R (R for repair) resulted in viable cultured trypanosomes that grew slower than normal. XPB-R depletion did not affect transcription in vivo or in vitro and XPB-R was not found to occupy the SLRNA promoter which assembles a RNA polymerase II transcription pre-initiation complex including TFIIH. However, XPB-R −/− cells were much less tolerant than wild-type cells to UV light- and cisplatin-induced DNAdamage, which require NER. Since XPB-R −/− cells were not impaired in DNA base excision repair, XPB-R appears to function specifically in NER. Interestingly, several other protists possess highly divergent XPB paralogs suggesting that XPBs specialized in transcription or NER exist beyond the Kinetoplastida.