Laboratory Ritwick Sawarkar

Laboratory Ritwick Sawarkar

Chromatin control of environmental stress response

A typical metazoan cell expresses only a fraction of all the genes it inherits from the mother cell. How does a cell decide which genes to express? Organisms have evolved sophisticated logical networks, which select genes for expression. An important element in these networks is chromatin that influences the activity of RNA polymerase enzyme complex. Over the past few years, it has been shown that RNA polymerase II (pol II) gets recruited to promoters of several genes, but pauses shortly thereafter. This appears to be a critical rate-limiting step for gene regulation.

The precise reasons and consequences of this event, especially in the context of chromatin, remain largely unknown. Furthermore, how misregulation of pol II pausing is instrumental in diseases such as cancer is unexplored. By employing systems biology, genetics and single cell approaches in Drosophila and mammalian systems, we will elucidate the basic principles of the crosstalk between chromatin and RNA pol II pausing.

Selected Publications

Rawat P, Boehning M, Hummel B, Aprile-Garcia F, Pandit AS, Eisenhardt N, Khavaran A, Niskanen E, Vos SM, Palvimo JJ, Pichler A, Cramer P and Sawarkar R (2021)
Stress-induced nuclear condensation of NELF drives transcriptional downregulation
Molecular Cell 81
Aprile-Garcia F,  Tomar P, Hummel B, Khavaran A & Sawarkar R (2019)
Nascent-protein ubiquitination is required for heat shock-induced gene downregulation in human cells
Nature Structural & Molecular Biology 26, 137-146
Hummel B, Hansen EC, Yoveva A, Aprile-Garcia F, Hussong R & Sawarkar R (2017)
The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses
Nature Structural & Molecular Biology, 30 January 2017 (AOP)

Our most recent publication Hummel et al. 2017 was

Sawarkar R and Paro R (2013)
Hsp90@chromatin.nucleus: an emerging hub of a networker.
Trends in Cell Biology 23(4), 193-201.

The article was chosen as one of the “Top 10 Editorial Board Favorites for 2013”.
Sawarkar R, Sievers C and Paro R (2012)
Hsp90 globally targets paused RNA polymerase to regulate gene expression in response to stimuli.
Cell 149(4), 807-818.
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