ISSN 10227954, Russian Journal of Genetics, 2011, Vol. 47, No. 4, pp. 394–403. © Pleiades Publishing, Inc., 2011.
Original Russian Text © V.G. Korolev, 2011, published in Genetika, 2011, Vol. 47, No. 4, pp. 449–459.
DNA is an informationally active chemical com
ponent of the cell genetic material. In view of this, it
seems that it should exhibit high stability in order to
effectively preserve genetic information. Surprisingly,
in reality the DNA primary structure is highly
dynamic and constantly changing. These changes are
induced by endogenous (methabolic processes) and
exogenous (environmental agents) factors. At the cel
lular level, ineffective DNA repair may lead to destabi
lization of the genome, apoptosis, aging, mutation,
and oncogenic transformation.
Efficiency of eliminating DNA lesions in eukary
otic cells is hindered by the fact that these lesions must
be detected and repaired within the highly condensed
chromatin. It is well known that these compact struc
tures substantially hinder DNA repair. This results in
necessity of nucleosome modification and remodula
tion and their accordance with the biochemical stages
of searching for and eliminating DNA lesions.
The last decade witnessed a revolution in our
understanding of the chromatin role in DNA metabo
lism. Earlier, the chromatin was regarded as a static
structure required for ordered compactization of the
genetic material. Although DNA packaging and its
closeness are indeed important chromatin functions,
to date it is evident that nucleosomes are dynamic
instructive particles that are involved in practically all
chromosomal processes. This is achieved through
highly ordered changes in the chromatin structure.
Each nucleosome contains 147 DNA base pairs
wound 1.7 times around the central core of eight his
tone proteins (an octamer consisting of two copies of
H2A, H2B, H3, and H4 histones each). Nucleosomes
are separated by linker regions of 20–110 nucleotides.
The linker regions contain histone H1 and various
nonhistone proteins. Histone H1 interacts with the
internucleosome DNA at the sites of its enter into and
exit from the nucleosome. Nucleosomes exhibit at
least three dynamic properties: change of composi
tion, covalent modifications, and movement along
Each core histone consists of the globular part pro
viding the histone–histone and histone–DNA inter
actions, and N and Cterminal “tail” motifs, which
serve as targets for posttranslational modifications.
Cells also contain alternative versions of the canonical
histones, differing in the aminoacid sequences. One
of these isoforms is histone H2AX, which differs from
the canonical H2A histone by the presence of a short
Cterminal tail. Nucleosomes containing canonical
histones are formed during replication, and nonca
nonical histones replace canonical ones in the course
of metabolic processes not associated with replication,
such as transcription and repair.
The properties of histones, and, consequently,
nucleosomes, can be changed by posttranslational
addition of slight chemical modifications, such as
acetyl, methyl, phosphate, ubiquitin, and sumo
groups, which provide regulation of various cellular
processes, including transcription, repair, replication,
etc. Modifying complexes add or remove covalent
modificators on particular residues of histone pro
teins, thus creating “flags” recognized by transcription
regulators and other factors. Each core histone con
tains several sites prone to modification. However,
most of these sites normally are not modified. For
instance, in yeasts histone H4 can be potentially
acetylated at four lysines (K5, K8, K12, and K16).
Notwithstanding, normally only 12% of histone H4 is
acetylated at all of the four sites; 13%, at three; 28%,
at two, and 36%, at one site .
Both histone acetylation and their methylation are
reversible. Eukaryotic genomes encode proteins such as
Chromatin and DNA Damage Repair
V. G. Korolev
Konstantinov Institute of Nuclear Physics, Gatchina, Leningrad region, 188300 Russia
Received May 12, 2010
—In eukaryotic cells, inheritance of both exact DNA sequence and its arrangement into the chromatin
is critical for maintaining stability of the genome. Various DNA lesions induced by endogenous and exogenous
factors make this maintanance problematic. To understand completely how cells resolve this problem the
knowledge on the nature of these lesions, their detection, and repair within the chromatin environment should
be integrated. Understanding of these processes is complicated by multiple types of DNA lesions and repair
pathways, as well as the intricate organization of the chromatin. Recent advances in all these directions help to
get insight on the repair regulation of DNA within the chromatin at the molecular and cellular level.