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Bruce Knutson, PhD

4257 Weiskotten Hall
766 Irving Avenue
Syracuse, NY 13210
Bruce Knutson's email address generated as an image


Associate Professor of Biochemistry and Molecular Biology




Biochemistry and Molecular Biology
Biomedical Sciences Program
Neuroscience and Physiology


RNA polymerase I transcription (structure, assembly, regulation), nucleolar biology, macromolecular architecture, crosslinking, proteomics, bioinformatics, modeling, molecular genetics, biochemistry, model systems



Fig.1. the nucleolus
Fig.1. The nucleolus

A century old hallmark of cancer is an enlarged nucleolus (Fig.1), a unique nuclear sub compartment where RNA polymerase I (Pol I) transcription and ribosome biogenesis take place. Pol I transcription is unregulated in cancer cells and drives cell proliferation, making it an attractive anti-cancer therapeutic target. The major focus of our research is to elucidate the molecular mechanism of Pol I transcription and how its dysregulation leads to cancer and disease. Our research uses an innovative cross-organismal and interdisciplinary approach that integrates bioinformatics, biochemistry, computational biology, genetics, proteomics and structural biology in yeast and human model system.

Molecular architecture of the Pol I preinitiation complex (PIC)

Fig. 2. Pol I PIC Model
Fig. 2. Pol I PIC Model

Pol I transcription begins with the formation of the PIC (Fig.2), a macromolecular assemblage of more than 20 different proteins that function coordinately to accurately position Pol I at the promoter and to help initiate transcription. We are interested in the key structural facets of Pol I PIC formation and how it's altered in cancer and diseased cells. Our lab uses an integrated combination of sophisticated protein-protein interaction mapping technologies such as combined chemical crosslinking/mass spectrometry to determine the spatial orientation of Pol I PIC components and how they change during the transcription cycle and in diseased states.

Pol I and craniofacial dysmorphology. Mutations in Pol I cause an autosomal dominant craniofacial abnormality called Treacher Collins Syndrome (TCS). TCS is characteried by an underdeveloped lower jaw and cheekbones that is treated by an extensive multi-stage surgical reconstruction from childhood to early adulthood. We are interested in how these Pol I mutations cause TCS, how they affect Pol I activity, and how they can be suppressed to prevent the disease. Currently, there are no known cures for TCS and other related craniofacial dysmorphologies.

Fig.3. Pol I Regulation
Fig.3. Pol I Regulation

Pol I dysregulation in cancer. The upregulation of Pol I transcription in cancer cells coincides with activating mutations in many oncogenes and loss of function mutations in tumor suppressors that are believed to directly regulate Pol I activity (Fig.3). However, their bona fide Pol I targets and sites of interaction remain unclear. To understand how these cancer proteins target the Pol I complex, we use a combination of protein crosslinking technologies coupled of molecular genetics and biochemistry to identify and characterize the direct and functionally relevant in vivo Pol I targets. These studies will illuminate new strategies to control aberrant Pol I activity.

Graduate research in the Knutson Lab. Interested students should directly contact Bruce Knutson to discuss available research opportunities.


Knutson BA, McNamar R, Rothblum LI. Dynamics of the RNA polymerase I TFIIF/TFIIE-like subcomplex: a mini-review. Biochem Soc Trans. 2020 Oct 30;48(5):1917-1927. doi: 10.1042/BST20190848.

Knutson BA, Smith ML, Belkevich AE, Fakhouri AM. Molecular Topology of RNA Polymerase I Upstream Activation Factor. Mol Cell Biol. 2020 Jun 15;40(13):e00056-20. doi: 10.1128/MCB.00056-20. Print 2020 Jun 15.

McNamar R, Abu-Adas Z, Rothblum K, Knutson BA, Rothblum LI. Conditional depletion of the RNA polymerase I subunit PAF53 reveals that it is essential for mitosis and enables identification of functional domains. J Biol Chem. 2019 Dec 27;294(52):19907-19922. doi: 10.1074/jbc.RA119.009902. Epub 2019 Nov

Jackobel AJ, Zeberl BJ, Glover DM, Fakhouri AM, Knutson BA. DNA binding preferences of S. cerevisiae RNA polymerase I Core Factor reveal a preference for the GC-minor groove and a conserved binding mechanism. Biochim Biophys Acta Gene Regul Mech. 2019 Sep;1862(9):194408. doi: 10.1016/j.bbagrm.2019.194408. Epub 2019 Aug 2.

Smith ML, Cui W, Jackobel AJ, Walker-Kopp N, Knutson. Reconstitution of RNA Polymerase I Upstream Activating Factor and the Roles of Histones H3 and H4 in Complex Assembly. J Mol Biol. 2018 Epub

Jackobel AJ, Han Y, He Y, Knutson BA. Breaking the mold: structures of the RNA polymerase I transcription complex reveal a new path for initiation. Transcription. 2018 Jan 15:1-7

Walker-Kopp N, Jackobel AJ, Pannafino GN, Morocho PA, Xu X, Knutson BA. Treacher Collins syndrome mutations in Saccharomyces cerevisiae destabilize RNA polymerase I and III complex integrity. Hum Mol Genet. 2017 Nov 1;26(21):4290-4300.

Han Y, Yan C, Nguyen THD, Jackobel AJ, Ivanov I, Knutson BA, He Y. Structural mechanism of ATP-independent transcription initiation by RNA polymerase I. Elife. 2017 Jun 17;6.

Knutson BA, Smith ML, Walker-Kopp N, Xu X. Super elongation complex contains a TFIIF-related subcomplex. Transcription. 2016. 7(4):133-40

Knutson BA, Lui J, Ranish J. Hahn S. Architecture of the S.cerevisiae RNA polymerase I Core Factor complex. Nature Structural and Molecular Biology. 2014. 21(9): 810-816

Knutson BA, Hahn S. TFIIB-related factors in RNA polymerase I transcription. Biochem Biophys Acta. 2013. 1829(3-4): 265-273

Knutson BA. Emergence and expansion of TFIIB-like factors in the plant kingdom. Gene. 2013. 526(1): 30-38

Knutson BA, Hahn S. Yeast Rrn7 and human TAF1B are TFIIB-related RNA polymerase I general transcription factors. Science. 2011. 33(6049): 1637-40

Knutson BA, Hahn S. Domains of Tra1 important for activator recruitment and transcription coactivator functions of SAGA and NuA4 complexes. Mol Cell Biol. 2011. 31(4): 818-831

Knutson BA. Insights into the domain and repeat architecture of target of rapamycin. J Struct Biol. 2010. 170(2): 354-63


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