Regulation of DNA Translocation Efficiency within the Chromatin Remodeler RSC/Sth1 Potentiates Nucleosome Sliding and Ejection

Cedric R Clapier; Margaret M Kasten; Timothy J Parnell; Ramya Viswanathan; Heather Szerlong; George Sirinakis; Yongli Zhang; Bradley R Cairns

doi:10.1016/j.molcel.2016.03.032

Regulation of DNA Translocation Efficiency within the Chromatin Remodeler RSC/Sth1 Potentiates Nucleosome Sliding and Ejection

Mol Cell. 2016 May 5;62(3):453-461. doi: 10.1016/j.molcel.2016.03.032.

Authors

Cedric R Clapier¹, Margaret M Kasten¹, Timothy J Parnell¹, Ramya Viswanathan¹, Heather Szerlong¹, George Sirinakis², Yongli Zhang², Bradley R Cairns³

Affiliations

¹ Department of Oncological Sciences, Huntsman Cancer Institute and Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
² Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
³ Department of Oncological Sciences, Huntsman Cancer Institute and Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. Electronic address: [email protected].

Abstract

The RSC chromatin remodeler slides and ejects nucleosomes, utilizing a catalytic subunit (Sth1) with DNA translocation activity, which can pump DNA around the nucleosome. A central question is whether and how DNA translocation is regulated to achieve sliding versus ejection. Here, we report the regulation of DNA translocation efficiency by two domains residing on Sth1 (Post-HSA and Protrusion 1) and by actin-related proteins (ARPs) that bind Sth1. ARPs facilitated sliding and ejection by improving "coupling"-the amount of DNA translocation by Sth1 relative to ATP hydrolysis. We also identified and characterized Protrusion 1 mutations that promote "coupling," and Post-HSA mutations that improve ATP hydrolysis; notably, the strongest mutations conferred efficient nucleosome ejection without ARPs. Taken together, sliding-to-ejection involves a continuum of DNA translocation efficiency, consistent with higher magnitudes of ATPase and coupling activities (involving ARPs and Sth1 domains), enabling the simultaneous rupture of multiple histone-DNA contacts facilitating ejection.

MeSH terms

Adenosine Triphosphate / metabolism
Binding Sites
Biological Transport
Cell Cycle Proteins / chemistry
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Chromatin Assembly and Disassembly*
DNA, Fungal / genetics*
DNA, Fungal / metabolism*
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Hydrolysis
Microfilament Proteins / genetics
Microfilament Proteins / metabolism
Mutation
Nuclear Proteins / chemistry
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Nucleosomes / enzymology*
Nucleosomes / genetics*
Protein Binding
Protein Interaction Domains and Motifs
Saccharomyces cerevisiae / enzymology*
Saccharomyces cerevisiae / genetics*
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Time Factors
Transcription Factors / chemistry
Transcription Factors / genetics
Transcription Factors / metabolism*

Substances

Cell Cycle Proteins
DNA, Fungal
DNA-Binding Proteins
Microfilament Proteins
Nuclear Proteins
Nucleosomes
RSC complex, S cerevisiae
Saccharomyces cerevisiae Proteins
Transcription Factors
Adenosine Triphosphate
STH1 protein, S cerevisiae

Abstract

MeSH terms

Substances

Grants and funding