Abstract

Recently, we demonstrated that yeast Pol II employs a distinct mechanism for CPD bypass (called A-rule) involving a conformational flexibility of its active center (the mobile trigger loop domain in Rpb1 subunit) facilitating accommodation of bulky lesions. We recently expanded this project to Pol II bypass of bulky cyclopurine (CyPn) oxidative damages in transcribed genes and to analysis of RTLS (RNA polymerase translesion synthesis) through the bulky lesions by mammalian (calf thymus, CT) Pol II. We also study transcription mechanisms enabling mammalian RNA polymerase II to transcribe through non-bulky oxidative DNA lesions such as 8-oxoguanine and 5-hydrohyuracil.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011202-09
Application #
9556489
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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