Molecular Mechanisms of RNA Dependent DNA Damage Response
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29 September 2022
4:00 PM - University Campus Bohunice (pavilion B11/ seminar room 132)
Speaker
Dr. Monika Gullerova
Associate Professor in Experimental Pathology
"Dr Monika Gullerova studied molecular biology at Comenius University in Bratislava, where she developed her passion for molecular biology and experimental oncology. After graduation, she moved to Vienna to conduct her PhD and to extend research interests in the basic science of transcriptional regulation.
In 2006 Monika joined Professor Nicholas Proudfoot’s laboratory in Oxford as Postdoctoral Fellow investigating functions of Cohesin and RNA interference pathways. During her postdoctoral studies she was awarded the L’Oreal/UNESCO Women in Science UK award and joined Exeter College as Staines Medical Research Fellow. Concurrently Monika conducted studies at Harvard Medical School and Kyoto University.
In 2013 Monika established her own laboratory in the Sir William Dunn School of Pathology in Oxford, funded by MRC’s Career Development Award. Her research group investigates DNA damage response, in particular how RNA mediates rapid and efficient DNA damage repair. She was awarded the Hugh Price Fellowship at Jesus College in 2015. More recently, Monika was awarded a prestigious Senior Research Fellowship by Cancer Research UK to fund her research on genome stability and its relevance to cancer."
Link to the Gullerova lab websites.
About the lecture
"Molecular Mechanisms of RNA Dependent DNA Damage Response"
Tudor Interacting Repair Regulator (TIRR) is an RNA binding protein and a negative regulator of the DNA repair factor P53 Binding Protein 1 (53BP1). In non-damage conditions, TIRR is bound to the Tudor domain of 53BP1. After DNA damage, TIRR and 53BP1 dissociate and 53BP1 binds the chromatin at the double strand break (DSB) through the Tudor and ubiquitination-dependent recruitment (UDR) domains to promote the non-homologous end joining repair pathway. The exact mechanistic details of this dissociation in response to DSBs are not known. Increasing evidence has implicated RNA as a crucial factor in the DNA damage response (DDR). Here we show that RNA is instrumental for the dissociation of TIRR/53BP1. Specifically, RNA with a hairpin secondary structure, produced by RNA polymerase II (RNAPII), promotes the TIRR/53BP1 complex separation in proximity to the DSB. Hairpin RNA binds to the same residues on TIRR as 53BP1, causing steric clashes. Furthermore, a synthetic hairpin RNA can stimulate TIRR/53BP1 dissociation in cells. Our results uncover a previously unknown role of DSB derived RNA in modulating a protein-protein interaction, and contribute to our understanding of 53BP1 regulation in DSB repair.
Registration for lunch with the speaker /for Ph.D. students/
The sponsored lunch usually takes place in the Campus River restaurant. Please meet the speaker and other students at 12:45 at the reception desk at the main entrance (building B22, see the map below).
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