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

A. O. Sperry, V. C. Blasquez, W. T. Garrard

Research output: Contribution to journalArticle

191 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)5497-5501
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number14
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • General

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