TY - JOUR
T1 - Dysfunction of chromosomal loop attachment sites
T2 - Illegitimate recombination linked to matrix association regions and topoisomerase II
AU - Sperry, A. O.
AU - Blasquez, V. C.
AU - Garrard, W. T.
PY - 1989
Y1 - 1989
N2 - A family of A+T-rich sequences termed MARs ('matrix association regions') mediate chromosomal loop attachment. Here we demonstrate that several MARs both specifically bind and contain multiple sites of cleavage by topoisomerase II, a major protein of the mitotic chromosomal scaffold. Interestingly, 'hotspots' of enzyme cutting occur within the MAR of the mouse immunoglobulin κ-chain gene at the breakpoint of a previously described chromosomal translocation. Since topoisomerase II can mediate illegitimate recombination in prokaryotes, we explored further the possibility that MARs might be targets for this process in eukaryotes. We found that a MAR had been deleted from one of the two rabbit immunoglobulin κ-chain genes and that MARs reside next to a long interspersed repetitive element within the recombination junction of a human ring chromosome 21. These results, taken together with other accounts of nonhomologous recombination, lead to the proposal that a dysfunction of MARs is illegitimate recombination.
AB - A family of A+T-rich sequences termed MARs ('matrix association regions') mediate chromosomal loop attachment. Here we demonstrate that several MARs both specifically bind and contain multiple sites of cleavage by topoisomerase II, a major protein of the mitotic chromosomal scaffold. Interestingly, 'hotspots' of enzyme cutting occur within the MAR of the mouse immunoglobulin κ-chain gene at the breakpoint of a previously described chromosomal translocation. Since topoisomerase II can mediate illegitimate recombination in prokaryotes, we explored further the possibility that MARs might be targets for this process in eukaryotes. We found that a MAR had been deleted from one of the two rabbit immunoglobulin κ-chain genes and that MARs reside next to a long interspersed repetitive element within the recombination junction of a human ring chromosome 21. These results, taken together with other accounts of nonhomologous recombination, lead to the proposal that a dysfunction of MARs is illegitimate recombination.
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U2 - 10.1073/pnas.86.14.5497
DO - 10.1073/pnas.86.14.5497
M3 - Article
C2 - 2546156
AN - SCOPUS:0344413285
SN - 0027-8424
VL - 86
SP - 5497
EP - 5501
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -