A twist defect mechanism for ATP-dependent translocation of nucleosomal DNA

Autor: Robert F Levendosky, Gregory D. Bowman, Ilana M. Nodelman, Jessica Winger
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Saccharomyces cerevisiae Proteins
Base pair
QH301-705.5
Xenopus
Science
Snf2 ATPase
S. cerevisiae
Saccharomyces cerevisiae
General Biochemistry
Genetics and Molecular Biology
Chromatin remodeling
chromatin remodeling
03 medical and health sciences
chemistry.chemical_compound
Adenosine Triphosphate
Biochemistry and Chemical Biology
Nucleosome
Twist
Biology (General)
DNA
Fungal
Adenosine Triphosphatases
twist defect
General Immunology and Microbiology
biology
Chemistry
Superhelix
DNA
Superhelical
General Neuroscience
nucleosome
DNA translocation
superfamily 2 ATPase
General Medicine
Chromosomes and Gene Expression
Chromatin
Nucleosomes
DNA-Binding Proteins
030104 developmental biology
Histone
biology.protein
Biophysics
Nucleic Acid Conformation
Medicine
DNA
Acyltransferases
Research Article
Zdroj: eLife, Vol 7 (2018)
eLife
Popis: As superfamily 2 (SF2)-type translocases, chromatin remodelers are expected to use an inchworm-type mechanism to walk along DNA. Yet how they move DNA around the histone core has not been clear. Here we show that a remodeler ATPase motor can shift large segments of DNA by changing the twist and length of nucleosomal DNA at superhelix location 2 (SHL2). Using canonical and variant 601 nucleosomes, we find that the Saccharomyces cerevisiae Chd1 remodeler decreased DNA twist at SHL2 in nucleotide-free and ADP-bound states, and increased twist with transition state analogs. These differences in DNA twist allow the open state of the ATPase to pull in ~1 base pair (bp) by stabilizing a small DNA bulge, and closure of the ATPase to shift the DNA bulge toward the dyad. We propose that such formation and elimination of twist defects underlie the mechanism of nucleosome sliding by CHD-, ISWI-, and SWI/SNF-type remodelers.
eLife digest DNA is shaped like a spiral staircase, twisting around itself to create a double helix. This results in a long string-like molecule that needs to be carefully packaged to fit inside the cells of organisms as diverse as fungi or humans. This packaging process starts when a portion of DNA tightly wraps around a spool-like core of proteins called histones. The resulting structure is known as a nucleosome. Like the beads on a necklace, nucleosomes exist at regular intervals along DNA. The DNA sequence around the histones cannot be accessed by a cell, and so the nucleosomes need to be ‘shifted’ along DNA to free up the genetic information. Enzymes known as chromatin remodelers perform this role by binding to a nucleosome, and then using energy to fuel a change in their structure that makes them ‘crawl’ on DNA like an inchworm. During this process, chromatin remodelers slide nucleosomes along the DNA, but it was unclear how exactly the inchworm motions pushed DNA around the histones. Here, Winger et al. look into the details of this mechanism by focusing on the chromatin remodeler Chd1, which is conserved from yeast to humans. Experiments show that, first, the enzyme slightly untwists the DNA double helix; this untwisting causes the DNA to pucker a little on the nucleosome. The puckering creates tension and ‘pulls’ DNA towards the remodeler. Then, Chd1 changes its structure and twists DNA in the opposite direction, which forces the puckered DNA onto the other side of the remodeler. This extra bit of DNA then propagates around the rest of the nucleosome, like the wave created by flicking the end of a long rope. This sheds light on how these enzymes can ratchet DNA past the histones. As the gatekeepers of our genetic information, chromatin remodelers are key to the health of the cell – in fact, they are often affected in cancers. The work by Winger et al. creates a framework that will help to understand how exactly chromatin remodelers help cells access the genetic information that the body needs to function properly.
Databáze: OpenAIRE
Externí odkaz: