The mechanism of TCR initiation in S. cerevisiae is distinct from the TCR initiation in mammalian cells. While deletion of the Cockayne Syndrome Group B gene severely inhibits TCR in the mammalian cells, deletion of its yeast homologue Rad26 only slightly impairs the TCR. Genetic analyses strongly suggest two alternative TCR subpathways in yeast. The first, dominant pathway is probably initiated by Pol II interaction with Rad26, and is dependent on a non-essential Pol II subunit Rpb4. The second TCR pathway becomes prominent in the absence of Rpb4, and is dependent on another non-essential Pol II subunit Rpb9. The mechanism of the Rpb9-mediated TCR pathway is not well understood. Its investigation by genetic means has been hampered by the lack of the RPB4/RPB9 double deletion mutant, which is likely to be lethal. Analysis of the Rpb9-dependent pathway in yeast may provide important insights into the Pol II-related events during TCR. The location of the Rpb9 subunit on the perimeter of Pol II suggests its possible function in recruiting NER factors to the damaged site. Rpb9 is involved in multiple-transcription related functions such as transcription initiation (selection of the start site), transcription elongation, and recently in ubiquitination and degradation of rpb1 in response to UV-induced DNA damage. This subunit also interacts with a plethora of factors involved in transcription elongation and histone modification (like TFIIS, TFIIE, and SAGA). Which of these factors act as a Rad26 analogue in the Rpb9-mediated TCR pathway remains to be identified.

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KIreeva, Maria; Trang, Cyndi; Matevosyan, Gayane et al. (2018) RNA-DNA and DNA-DNA base-pairing at the upstream edge of the transcription bubble regulate translocation of RNA polymerase and transcription rate. Nucleic Acids Res 46:5764-5775
Kireeva, Maria L; Afonin, Kirill A; Shapiro, Bruce A et al. (2017) Cotranscriptional Production of Chemically Modified RNA Nanoparticles. Methods Mol Biol 1632:91-105
Bubunenko, Mikhail G; Court, Carolyn B; Rattray, Alison J et al. (2017) A Cre Transcription Fidelity Reporter Identifies GreA as a Major RNA Proofreading Factor in Escherichia coli. Genetics 206:179-187
Herrera-Asmat, Omar; Lubkowska, Lucyna; Kashlev, Mikhail et al. (2017) Production and characterization of a highly pure RNA polymerase holoenzyme from Mycobacterium tuberculosis. Protein Expr Purif 134:1-10
Walmacq, Celine; Wang, Lanfeng; Chong, Jenny et al. (2015) Mechanism of RNA polymerase II bypass of oxidative cyclopurine DNA lesions. Proc Natl Acad Sci U S A 112:E410-9
Sun, Bo; Pandey, Manjula; Inman, James T et al. (2015) T7 replisome directly overcomes DNA damage. Nat Commun 6:10260
Imashimizu, Masahiko; Shimamoto, Nobuo; Oshima, Taku et al. (2014) Transcription elongation: Heterogeneous tracking of RNA polymerase and its biological implications. Transcription 5:
Imashimizu, Masahiko; Shimamoto, Nobuo; Oshima, Taku et al. (2014) Transcription elongation. Heterogeneous tracking of RNA polymerase and its biological implications. Transcription 5:e28285
Walmacq, Celine; Cheung, Alan C M; Kireeva, Maria L et al. (2012) Mechanism of translesion transcription by RNA polymerase II and its role in cellular resistance to DNA damage. Mol Cell 46:18-29
Walmacq, Celine; Kireeva, Maria L; Irvin, Jordan et al. (2009) Rpb9 subunit controls transcription fidelity by delaying NTP sequestration in RNA polymerase II. J Biol Chem 284:19601-12