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PMID: 17515608 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Interchromosomal crossover in human cells is associated with long gene conversion tracts.

Molecular and cellular biology ·Vol. 27 ·No. 15 ·2007-08-00 ·Pages 5261-74

Neuwirth EA, Honma M, Grosovsky AJ

Abstract

Crossovers have rarely been observed in specific association with interchromosomal gene conversion in mammalian cells. In this investigation two isogenic human B-lymphoblastoid cell lines, TI-112 and TSCER2, were used to select for I-SceI-induced gene conversions that restored function at the selectable thymidine kinase locus. Additionally, a haplotype linkage analysis methodology enabled the rigorous detection of all crossover-associated convertants, whether or not they exhibited loss of heterozygosity. This methodology also permitted characterization of conversion tract length and structure. In TI-112, gene conversion tracts were required to be complex in tract structure and at least 7.0 kb in order to be selectable. The results demonstrated that 85% (39/46) of TI-112 convertants extended more than 11.2 kb and 48% also exhibited a crossover, suggesting a mechanistic link between long tracts and crossover. In contrast, continuous tracts as short as 98 bp are selectable in TSCER2, although selectable gene conversion tracts could include a wide range of lengths. Indeed, only 16% (14/95) of TSCER2 convertants were crossover associated, further suggesting a link between long tracts and crossover. Overall, these results demonstrate that gene conversion tracts can be long in human cells and that crossovers are observable when long tracts are recoverable.

MeSH Terms
Alleles Cell Line, Tumor Chromosome Segregation/genetics Chromosomes, Human/genetics Crossing Over, Genetic/genetics Deoxyribonucleases, Type II Site-Specific/metabolism Gene Conversion/genetics Genetic Linkage Genetic Markers Humans Loss of Heterozygosity/genetics Models, Genetic Saccharomyces cerevisiae Proteins
Chemicals
Genetic Markers Saccharomyces cerevisiae Proteins AI4 protein, S cerevisiae Deoxyribonucleases, Type II Site-Specific
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Neuwirth Efrem A H
University of California, Department of Cell Biology and Neuroscience and Environmental Toxicology Graduate Program, 2211 Biological Sciences Building, Riverside, CA 92521, USA.
Honma Masamitsu
Grosovsky Andrew J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.01852-06
Published
2007-08-00
Epub
2007-00-21
Pages
5261-74
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1952082
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.01852-06 PMC Full Text View journal details
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