In plant- and animal cells three quarter of the DNA is wrapped onto
protein cylinder (so-called histone octamers) forming so-called nucleosomes. DNA is wrapped nearly
twice around each cylinder and the resulting spool is connected to the
next spool via a portion of linker DNA. It is still a big puzzle how the
molecular machinery of the cell is able to access DNA in order to
transcribe genes, duplicate or repair DNA.
Our research on nucleosomes focuses on possible mechanisms that allow
transient access to DNA: (1) Nucleosome breathing, (2) force-induced unwrapping and
(3) nucleosome sliding.
(1) Thermal fluctuations can lead to spontaneous DNA unwrapping from one
of the ends of the wrapped portion. We study theoretically how one
can learn about the nucleosome energetics by measuring the accessibility
of DNA binding proteins to their target sequence inside a nuclesome.
Our findings can be interpreted in the light of new experiments on
force-induced unwrapping.
(2) We demonstrated that such an enforced unwrapping goes via the flipping of
the proteincylinder by 180 degrees, a process that goes over a
substantial energy barrier, see figure. In order to describe the
experimental data we needed to assume an effective repulsion between the
2 DNA turns. This explains how the nucleosome can spontaneously make its
DNA accessible by unwrapping one turn but holding a strong grip to the
other turn.
(3) Nucleosomes can also slide along DNA, a process that is made possible
by twist- or bulge defect that spontaneously form on the wrapped DNA
portion and propagate through the nucleosome. This mobility has
implications for many processes, e.g. when a transcribing RNA polymerase
encounters a nucleosome.
Check out some of our contributions:
I. Kulic and H. Schiessel: DNA spools under tension, Phys. Rev. Lett.
92, 228101 (2004)
F. Mohammad-Rafiee, I. M. Kulic and H. Schiessel, Theory of nucleosome
corkscrew sliding in the presence of synthetic DNA ligands, J. Mol.
Biol. 344, 47-58 (2004)
L. Mollazadeh-Beidokhti, F. Mohammad-Rafiee and H. Schiessel: Active
nucleosome displacement: a theoretical approach, Biophys. J. 96, 777-784 (2009)
P. Prinsen and H. Schiessel:
Nucleosome stability and accessibility of its DNA to proteins, Biochimie 92, 1722-1728 (2010)
