Minimal Cylinder Analysis Reveals the Mechanical Properties of Oncogenic Nucleosomes

Autor:	Pitman, Mary, Dalal, Yamini, Papoian, Garegin A.
Rok vydání:	2019
Předmět:	Physics - Biological Physics Quantitative Biology - Biomolecules Quantitative Biology - Genomics
Druh dokumentu:	Working Paper
DOI:	10.1016/j.bpj.2020.01.042
Popis:	Histone variants regulate replication, transcription, DNA damage repair, and chromosome segregation. Though widely accepted as a paradigm, it has not been rigorously demonstrated that histone variants encode unique mechanical properties. Here, we present a new theoretical approach called Minimal Cylinder Analysis (MCA) to determine the Young's modulus of nucleosomes from all-atom Molecular Dynamics (MD) simulations. Recently, we validated this computational analysis against in vitro single-molecule nanoindentation of histone variant nucleosomes. In this report, we further extend MCA to study the biophysical properties of hybrid nucleosomes that are known to exist in human cancer cells and contain H3 histone variants CENP-A and H3.3. We investigate the mechanism by which the elasticity of these heterotypic nucleosomes augments cryptic binding surfaces. Further, we derive biological predictions that might arise when such heterotypic nucleosomes take over large parts of the genome. Comment: 37 pages, 3 figures
Databáze:	arXiv
Externí odkaz:	http://arxiv.org/abs/1910.10247 Zobrazit plný text záznamu View this record from Arxiv