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PMID: 2550794 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Comparison of filler DNA at immune, nonimmune, and oncogenic rearrangements suggests multiple mechanisms of formation.

Molecular and cellular biology ·Vol. 9 ·No. 7 ·1989-07-00 ·Pages 3049-57

Roth DB, Chang XB, Wilson JH

Abstract

Extra nucleotides (termed filler DNA) are commonly found at the junctions of genetic rearrangements in mammalian cells. The filler DNA at immune system rearrangements, which are called N regions, are generated at VDJ joints primarily by terminal deoxynucleotidyl transferase. However, the origin of filler DNA at genetic rearrangements in nonlymphoid cells is uncertain. In an analysis of more than 200 junctions that arose by circularization of transfected linear DNA (D. B. Roth and J. H. Wilson, Mol. Cell. Biol. 6:4295-4304, 1986), we found 18 junctions with extra nucleotides exactly at the point of circularization. Analysis of these 18 junctions indicated that nonlymphoid cells could add extra nucleotides to the ends of duplex DNA. The characteristics of the extra nucleotides at these junctions and at 31 other rearrangement junctions from nonlymphoid cells were quite similar, suggesting that many genetic rearrangements may pass through a stage with free DNA ends. A comparison of the filler DNA at these 49 nonimmune system rearrangements with 97 N regions derived from immune system rearrangements suggested that lymphoid and nonlymphoid cells use different mechanisms for insertion of filler DNA, as expected from the absence of detectable terminal deoxynucleotidyl transferase in cells from nonlymphoid tissues. The filler DNAs at a smaller group of 22 translocations associated with cancer had features in common with both immune and nonimmune system rearrangements and therefore may represent a mixture of these two processes. Mechanisms that might account for the presence of filler DNA in nonlymphoid cells are discussed.

MeSH Terms
Animals Base Composition Base Sequence Cell Line DNA/genetics,metabolism DNA, Recombinant DNA, Viral/genetics,metabolism DNA-Directed DNA Polymerase/genetics,metabolism Gene Rearrangement Genes, Immunoglobulin Mammals/genetics Molecular Sequence Data Simian virus 40/genetics Transfection Translocation, Genetic Viral Plaque Assay
Chemicals
DNA, Recombinant DNA, Viral DNA DNA-Directed DNA Polymerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Roth D B
Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030.
Chang X B
Wilson J H
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1989-07-00
Pages
3049-57
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC362774
Subset
IM
Grants
NCI NIH HHS · CA15743 · United States
NIGMS NIH HHS · GM33405 · United States
NIGMS NIH HHS · GM38219 · United States
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