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@article{224656,
author = {Kozubek, Stanislav and Lukášová, Emilie and Rýznar, Leonard and Kozubek, Michal and Govorun, Raisa and Krasavin, Evgenij and Horneck, Gerda},
article_number = {12},
keywords = {nuclear topography; ABL; BCR},
language = {eng},
issn = {0006-4971},
journal = {Blood},
title = {Distribution of ABL and BCR genes in cell nuclei of normal and irradiated lymphocytes},
volume = {89},
year = {1997}
}
TY - JOUR
ID - 224656
AU - Kozubek, Stanislav - Lukášová, Emilie - Rýznar, Leonard - Kozubek, Michal - Govorun, Raisa - Krasavin, Evgenij - Horneck, Gerda
PY - 1997
TI - Distribution of ABL and BCR genes in cell nuclei of normal and irradiated lymphocytes
JF - Blood
VL - 89
IS - 12
SP - 4537
EP - 4537
SN - 00064971
KW - nuclear topography
KW - ABL
KW - BCR
N2 - Using dual-color fluorescence in situ hybridization (FISH) combined with two-dimensional (2D) image analysis, the locations of ABL and BCR genes in cell nuclei were studied. The center of nucleus-to-gene and mutual distances of ABL and BCR genes in interphase nuclei of nonstimulated and stimulated lymphocytes as well as in lymphocytes stimulated after irradiation were determined. We found that, after stimulation, the ABL and BCR genes move towards the membrane, their mutual distances increase, and the shortest distance between heterologous ABL and BCR genes increases. The distribution of the shortest distances between ABL and BCR genes in the G0 phase of lymphocytes corresponds to the theoretical distribution calculated by the Monte-Carlo simulation. Interestingly, the shortest ABL-BCR distances in G1 and S(G2) nuclei are greater in experiment as compared with theory. This result suggests the existence of a certain regularity in the gene arrangement in the G1 and S(G2) nuclei that keeps ABL and BCR genes at longer than random distances. On the other hand, in about 2% to 8% of lymphocytes, the ABL and BCR genes are very close to each other (the distance is less than 0.2 to 0.3 ľm). For comparison, we studied another pair of genes, c-MYC and IgH, that are critical for the induction of t(8;14) translocation that occurs in the Burkitt's lymphoma. We found that in about 8% of lymphocytes, c-MYC and IgH are very close to each other. Similar results were obtained for human fibroblasts. Gamma-radiation leads to substantial changes in the chromatin structure of stimulated lymphocytes: ABL and BCR genes are shifted to the nuclear center, and mutual ABL-BCR distances become much shorter in the G1 and S(G2) stages of the cell cycle. The fact that the genes involved in the t(8;14) translocation are also located close together in a certain fraction of cells substantiates the hypothesis that physical distance plays an important role in the processes leading to the translocations that are responsible for oncogenic transformation of cells.
ER -
KOZUBEK, Stanislav, Emilie LUKÁŠOVÁ, Leonard RÝZNAR, Michal KOZUBEK, Raisa GOVORUN, Evgenij KRASAVIN and Gerda HORNECK. Distribution of ABL and BCR genes in cell nuclei of normal and irradiated lymphocytes. \textit{Blood}. 1997, vol.~89, No~12, p.~4537-4545. ISSN~0006-4971.
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