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New roles for ATP-dependent chromatin remodelers at transcription-replication conflicts [IRB Research Nodes Seminar]

IRB Barcelona BioMed Seminars
7 Apr 21

Speaker: Aleix Bayona-Feliu Ph.D.

Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Sevilla, Spain / Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Spain

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Presentation


 

Host: Núria López-Bigas & Ferran Azorin

Organizer: Computational Biology / Cell Pathophysiology Nodes

Date: Wednesday 7 April 2021, 12.00h

 

ABSTRACT:

Transcription-replication conflicts are harmful situations that may occur naturally and pose an important source of endogenous DNA damage if not properly addressed by the cell machinery. R loops are three stranded nucleic acid structures composed by a DNA:RNA hybrid and a displaced ssDNA strand that may form co-transcriptionally and impede DNA replication fork progression. Chromatin dynamics are emerging as key players in preventing R loop-mediated genome instability. Chromatin structure and function are mainly regulated through the action of ATP-dependent chromatin remodelers which are frequently found altered in cancer. Particularly, the SWI/SNF complex harbors some of the most frequently mutated factors in cancer. Therefore, we have studied the effect of knocking-down BRG1, the ATPase subunit of SWI/SNF complex, on genome stability. Here we provide experimental evidence for the involvement of SWI/SNF complex in preventing R loop accumulation and R loop-derived genomic instability in HeLa and K562 cells using specific functional assays as well as genome-wide approaches. Our results open new relevant insights to our understanding of the role of chromatin remodelers in the control R loop homeostasis and its impact on genome integrity. Importantly, we unveil one underlying mechanism that could explain the high SWI/SNF complex mutation frequency found in cancer.