Stage M1S2 (2021-2022)

In eukaryotes, DNA is made to fit inside the cell nucleus through a high degree of compaction that is enabled by assembly into chromatin. Processes such as DNA damage repair and transcription require localized changes in chromatin compaction. Cells have multiple molecular strategies to control this. In one, multi-protein chromatin remodelling complexes use the energy from ATP hydrolysis to alter DNA compaction. Among them, the mammalian SWI/SNF complex is of special interest because a number of proteins were recently discovered as core components unique to the human complex, but the role they play within mSWI/SNF is unknown and these subunits are coded by genes mutated or miss-expressed in many forms of cancers. By using protein crystallography, cryo-EM, proteomics, in vitro and in cell assays we aim at determining the function and the 3D structure of these subunits. We aim at better understanding their function and determining the effect the malfunction of these subunits in malignancies.