Koltovaya - jinr :: laboratory of radiation biology

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GENOME STABILITY: GENETIC AND EPIGENETIC FACTORS
N.A. Koltovaya
Joint Institute for Nuclear Research, Dubna, Moscow Region, Russia
The report is dedicated to the 70th anniversary of geneticist Alexander Devin's birth
(1944—2007). An important field of his work was studying the genetic control of the
stability of Saccharomyces cerevisiae yeast's genome and a search for new genes determining
cell genetic stability. Saccharomycete yeasts are especially convenient for genome stability
research because they are tolerant to extra chromosomes. Besides, by the beginning of this
work, the mitochondrial genome was most studied in yeasts among all eukaryotes because
yeast cells can survive its degenerative rearrangements (rho-) and even elimination (rho0). A
special method was developed that allowed making a collection of nuclear mutations leading
to a change in the stability of the nuclear and mitochondrial genomes (Devin, Koltovaya,
1981; Devin et al., 1994). These mutations increased the chromosome loss frequency in
aneuploid strains and decreased the mitochondrial mutation (rho-) frequency. It was also
found that aneuploidy has a regulating effect on mitochondrial genome stability (Devin et al.,
1987). It is remarkable those for the first time mutations were obtained that stabilize the
mitochondrial genome and decrease the respiratory failure mutation frequency. The nature of
this phenomenon is still unclear and is very interesting.
To understand how these enzymes control genome stability and in what processes
they participate, genetic appearances of mutations were studied (Devin et al., 1990;
Koltovaya et al., 2003; Koltovaya et al., 1998; Koltovaya, Kadyshevskaya, 2009). Besides
chromosome destabilization, found were mutation influence on cell sensitivity to the
damaging effect of ionizing radiation, DNA recombination and checkpoints. Among the
studied mutations, isolated were the mutations leading to cell radiosensitivity and
radioresistance.
Some of the nuclear mutations were mapped and sequenced (Devin et al., 1990;
Koltovaya et al., 2003). It turned out that the studied mutations are localized in highly
hierarchical genes that play the key role in cell functioning. In terms of modern system
biology, those are the so-called hubs of biological networks describing the physical
interactions between the proteins. The identified genes participate in the regulation of cell
processes by chemical modifications. One of them encodes the central CDC28/CDK1 kinase,
which regulates cell cycle transition (Koltovaya, 2013). The second gene encodes the Ada1
component of the transcriptional histonacetyltransferase complex SAGA, in which it is the
Gcn5 subunit that has acetylase activity. The third gene encodes the nucleolar Net1 protein,
which controls Sir2 deacetylase localization. It was supposed that the observed effects are
determined by the chemical modification of different substrates in particular chromatin
structure elements (phosphorylation, acetylation, and deactylation of histones and nonhistone proteins), and that there exist common regulatory elements of nuclear and
mitochondrial DNA chromosome packing. It is interesting how the results obtained by A.B.
Devin and his colleagues match modern data and how they were developed. The report will
include a review of literature data on the epigenetic regulation of the molecular cell processes
involving mentioned genes.
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Devin A.B., Koltovaya N.A. (1981) Mutation Res. 91: 451—455.
Devin A.B., Koltovaya N.A., Gavrilov B.V., Arman I.P. (1994) J. Rus. Genetics 30: 1194—1201.
Devin A.B., Koltovaya N.A., Cheryomukhina N.I. (1987) Curr. Genet. 11: 407—410.
Devin A.B., Prosvirova T.Yu., Peshkonov V.T., et al. (1990) Yeast 6: 231—243.
Koltovaya N.A., Guerasimova A.S., Tchekhouta I.A., Devin A.B. (2003) Yeast 20: 955—-971.
Koltovaya N.A., Arman I.P., Devin A.B. (1998) Yeast 14: 133—146.
Kotlovaya N.A., karviga T.D., Lubimova K.A., et al. (1998). J. Rus. Genetics 34: 610—624.
Kadishevskaya E.Yu., Koltovaya N.A. (2009) J. Rus. Genetics 45: 458—470.
Koltovaya N.A. (2013) J. Rus. Genetics 49: 797—813.
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