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Critical Reviews™ in Eukaryotic Gene Expression

Impact factor: 1.660

ISSN Print: 1045-4403
ISSN Online: 2162-6502

Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v20.i3.10
pages 181-194

Genome Instability in the Context of Chromatin Structure and Fragile Sites

Eva Bartova
Institute of Biophysics, Academy of Sciences of the Czech Republic
Gabriela Galiova
Institute of Biophysics, Academy of Sciences of the Czech Republic
Sona Legartova
Institute of Biophysics, Academy of Sciences of the Czech Republic
Lenka Stixova
Institute of Biophysics, Academy of Sciences of the Czech Republic
Alzbeta Jugova
Institute of Biophysics, Academy of Sciences of the Czech Republic
Stanislav Kozubek
Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic

ABSTRACT

Genomes are exposed to various external stimuli that induce DNA damage in the form of single- or double-stranded DNA breaks. Fragile sites in the human genome are sensitive to genotoxic stress and, when not appropriately repaired, are responsible for chromosomal aberrations, including the gene amplifications observed in a variety of tumors. Moreover, when DNA lesions from different chromosomes are in close proximity and not repaired, the probability of chromosome translocations is greatly increased. These events can be induced by ionizing radiation that, in a majority of cells, induces a G2/M cell cycle arrest and is characterized by the repositioning of many tumor-related genes closer to the nuclear interior. On the basis of this knowledge, we review functional and structural aspects of chromosomal rearrangements and the DNA repair machinery.