Question

I generated 2 mutations in the catalytic subunit of the SWI/SNF chromatin remodeler, and tested for binding of SWI/SNF to nucleosomes using a gel retardation assay and plotted a graph of % nucleosomes bound vs increase in protein concentration for each mutant. If A is WT SWI/SNF and B and C are mutations in the catalytic subunit, which mutation is likely to allow SWI/SNF to do its job BETTER as an ATP dependent chromatin remodeler?

Answer 1

SWI/SNF is a remodeler that uses adenosine triphosphate-hydrolysis to alter histone–DNA interactions, resulting in the histone octamer sliding along DNA or a complete removal of the octamer from DNA. It is responsible for various function which includes normal development of an organism . any mutation in SWI/SNF complex lead to cancer as well as neurological disorder.

SWI/SNF complex can be classified into three categories, namely (a) enzymatic subunits having catalytic ATPase activity including the Brahma homologue (BRM, encoded by SMARCA2) and BRMrelated gene 1 (BRG1, encoded by SMARCA4), (b) set of highly conserved ‘core’ subunits (SNF5 (also known as, INI1 or BAF47 encoded by SMARCB1), BAF155 and BAF170) and (c) accessory subunits that may contribute towards complex specificity (ARID1A/ARID1B, ARID2 .Only a set of four subunits (BRG1/SMARCA4,SNF5/ SMARCB1, BAF155/SMARCC1 and BAF170/SMARCC2) in humans is necessary and sufficient to perform chromatin Remodeling in vitro.

BRG1 and BRM non synonymous mutation of catalytic subunit that is change in aminoacid resulting alter conformation lead to decrease in Remodeling activity SWI/SNF complex while in case of synonymous mutation lead to change in codon but same amino acid at that position leading to normal type SWI/SNF complex with wild type function.