Ústav fyzikální chemie J. Heyrovského AV ČR, v.v.i.
Dolejškova 2155/3, 182 23 Praha 8
IČ: 61388955, DIČ: CZ61388955
Nucleic acid interactions and genome stability
Submitted by RNDr. Ctirad Hofr, Ph. D.
“Oponentský posudek habilitační práce”
The habilitation work of Ctirad Hofr is divided into three parts. The first part deals
with the “description of changes in structure and thermodynamics of DNA induced by the
binding of new and clinically used anticancer drugs derived from metal compounds“. In this
chapter the interaction of cisplatin, transplatin, and other metal-based potential anti-cancer
compounds with DNA (and to some limited extent also with DNA binding proteins) are
investigated. The methods used are mainly differential scanning calorimetry, (temperaturedependent)
UV absorption spectroscopy and circular dichroism determinations. Intellectually
these studies started with a comparison of cisplatin with its (in terms of cancer therapy
inactive) isomer transplatin and then was extended to further compounds, partially derived
from cispaltin. This chapter is based on 8 original publications in international impacted
journal (and one review in a Czech journal). This chapter has to be considered as the main
chapter of this habilitation thesis for following reasons: 1) More than half (8 out of 15) of the
all papers summarized in this thesis are devoted to this topic. 2) In 3 papers Ctirad Hofr is the
first author, and thus his exposed contributions to these papers are documented. The mainly
biophysical results described here are interesting and certainly internationally well
recognized. The second chapter investigates the interaction of (full-length human, plant, and
yeast) telomeric proteins with DNA. The methods used here are isothermal titration
calorimetry, surface plasmon resonance, electrophoretic techniques, and fluorescence
anisotropy based binding assays. This chapter is based on 4 original publications and an
overview article in a Czech based journal. In one paper Ctirad Hofr is the first author and in a
recently submitted one the corresponding author. Again, internationally recognized results are
presented and Ctirad Hofr’s contributions to those papers are evidently significant. In the
third chapter it is “demonstrated how functional binding studies and molecular structure data
are combined to obtain a more comprehensive and detailed view of mechanism of doublestranded
RNA recognition”, summarized in 3 original papers. Although these papers
appeared in very prestigious journals like Cell, Journal of Biological Chemistry or Genes and
Development, I consider this chapter more as an addition than a crucial, decisive part of this
habilitation thesis. Why? It is evident that for all 3 papers Dr. Hofr performed solely the
steady-sate fluorescence anisotropy experiments, which represent only a fragment in those
comprehensive studies based on a large variety of molecular biological, biochemical,
spectroscopic, and computational methods. Moreover, it is very likely that Richard Stefl
and/or Frederic Allain, and not Dr. Hofr are here the intellectual fathers of those
contributions.
Concluding, I would like to state that the habilitation thesis submitted by Dr. Hofr
is fulfilling in terms of publications the criteria for a successful habilitation procedure at
the “Masarykova Unverzita” in Brno. Consequently, I recommend accepting the
submitted thesis as a part of the habilitation procedure at that university.
Praha, 3.09.2014
Prof. Dr. Martin Hof, DSc
Vice-Director, Jaroslav Heyrovký Institute of Physical
Chemistry
Academy of Sciences of the Czech Republic
Phone: +420266053264
e-mail: martin.hof@jh-inst.cas.cz