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PMID: 2546156 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Dysfunction of chromosomal loop attachment sites: illegitimate recombination linked to matrix association regions and topoisomerase II.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 14 ·1989-07-00 ·Pages 5497-501

Sperry AO, Blasquez VC, Garrard WT

Abstract

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 kappa-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 kappa-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.

MeSH Terms
Animals Base Sequence Chromosome Mapping Cloning, Molecular DNA Topoisomerases, Type II/metabolism DNA, Recombinant/metabolism Drosophila/enzymology Genes, Immunoglobulin HeLa Cells/enzymology Humans Immunoglobulin kappa-Chains/genetics Mice Molecular Sequence Data Rabbits Recombination, Genetic Restriction Mapping
Chemicals
DNA, Recombinant Immunoglobulin kappa-Chains DNA Topoisomerases, Type II
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sperry A O
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
Blasquez V C
Garrard W T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.14.5497
Published
1989-07-00
Pages
5497-501
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC297650
Subset
IM
Grants
NIGMS NIH HHS · GM22201 · United States
NIGMS NIH HHS · GM29935 · United States
NIGMS NIH HHS · GM31689 · United States
External Links
PubMed source DOI: 10.1073/pnas.86.14.5497 PMC Full Text View journal details
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