Biochemistry & Molecular Pharmacology
Program in Molecular Medicine
Amino Acids, Peptides, and Proteins | Biochemistry | Enzymes and Coenzymes
Heterochromatin is a specialized chromatin structure that is central to eukaryotic transcriptional regulation and genome stability. Despite its globally repressive role, heterochromatin must also be dynamic, allowing for its repair and replication. In budding yeast, heterochromatin formation requires silent information regulators (Sirs) Sir2p, Sir3p, and Sir4p, and these Sir proteins create specialized chromatin structures at telomeres and silent mating-type loci. Previously, we found that the SWI/SNF chromatin remodeling enzyme can catalyze the ATP-dependent eviction of Sir3p from recombinant nucleosomal arrays, and this activity enhances early steps of recombinational repair in vitro. Here, we show that the ATPase subunit of SWI/SNF, Swi2p/Snf2p, interacts with the heterochromatin structural protein Sir3p. Two interaction surfaces are defined, including an interaction between the ATPase domain of Swi2p and the nucleosome binding, Bromo-Adjacent-Homology domain of Sir3p. A SWI/SNF complex harboring a Swi2p subunit that lacks this Sir3p interaction surface is unable to evict Sir3p from nucleosomes, even though its ATPase and remodeling activities are intact. In addition, we find that the interaction between Swi2p and Sir3p is key for SWI/SNF to promote resistance to replication stress in vivo and for establishment of heterochromatin at telomeres.
BAH, SWI/SNF, chromatin remodeling, Sir3, heterochromatin
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DOI of Published Version
Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):17827-32. doi: 10.1073/pnas.1420096111. Epub 2014 Dec 1. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Manning, Benjamin J. and Peterson, Craig L., "Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme" (2014). GSBS Student Publications. 1891.