GSBS Student Publications

Student Author(s)

Benjamin Manning

GSBS Program

Biochemistry & Molecular Pharmacology

Publication Date

2014-12-16

UMMS Affiliation

Program in Molecular Medicine

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry | Enzymes and Coenzymes

Abstract

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.

Keywords

BAH, SWI/SNF, chromatin remodeling, Sir3, heterochromatin

Rights and Permissions

Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.

DOI of Published Version

10.1073/pnas.1420096111

Source

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

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Comments

Supporting information and the dataset for this paper are available under "Additional Files."

Related Resources

Link to Article in PubMed

PubMed ID

25453095

pnas.201420096SI.pdf (1106 kB)
Supporting Information

pnas.1420096111.sd01.xlsx (680 kB)
Dataset S1. RNA-seq gene expression analysis of SWI2 and swi2–Δ10R

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