Home LiteratureArticle Details
PMID: 1549110 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Formation of heteroduplex DNA during mammalian intrachromosomal gene conversion.

Molecular and cellular biology ·Vol. 12 ·No. 4 ·1992-04-00 ·Pages 1546-52

Bollag RJ, Elwood DR, Tobin ED, Godwin AR, Liskay RM

Abstract

We have studied intrachromosomal gene conversion in mouse Ltk- cells with a substrate designed to provide genetic evidence for heteroduplex DNA. Our recombination substrate consists of two defective chicken thymidine kinase genes arranged so as to favor the selection of gene conversion products. The gene intended to serve as the recipient in gene conversion differs from the donor sequence by virtue of a palindromic insertion that creates silent restriction site polymorphisms between the two genes. While selection for gene conversion at a XhoI linker insertion within the recipient gene results in coconversion of the nearby palindromic site in more than half of the convertants, 4% of convertant colonies show both parental and nonparental genotypes at the polymorphic site. We consider these mixed colonies to be the result of genotypic sectoring and interpret this sectoring to be a consequence of unrepaired heteroduplex DNA at the polymorphic palindromic site. DNA replication through the heteroduplex recombination intermediate generates genetically distinct daughter cells that comprise a single colony. We believe that the data provide the first compelling genetic evidence for the presence of heteroduplex DNA during chromosomal gene conversion in mammalian cells.

MeSH Terms
Animals Blotting, Southern Cell Line Clone Cells Gene Conversion Genetic Markers Mice Nucleic Acid Heteroduplexes/biosynthesis Nucleic Acid Hybridization Polymorphism, Genetic Recombination, Genetic Selection, Genetic
Chemicals
Genetic Markers Nucleic Acid Heteroduplexes
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bollag R J
Department of Genetics and Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Elwood D R
Tobin E D
Godwin A R
Liskay R M
References (33)
33 references, click to expand
  1. Fungal recombination.
    Microbiol Rev. 1985 Mar;49(1):33-58 PMID: 3884994
  2. Introduction of homologous DNA sequences into mammalian cells induces mutations in the cognate gene.
    Nature. 1986 Nov 6-12;324(6092):34-8 PMID: 3785372
  3. Processing of complex heteroduplexes in Escherichia coli and Cos-1 monkey cells.
    Proc Natl Acad Sci U S A. 1984 Sep;81(18):5792-6 PMID: 6091108
  4. The nucleotide sequence of the chicken thymidine kinase gene and the relationship of its predicted polypeptide to that of the vaccinia virus thymidine kinase.
    Nucleic Acids Res. 1984 May 11;12(9):3959-71 PMID: 6328447
  5. Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process.
    Mol Cell Biol. 1984 Jun;4(6):1020-34 PMID: 6330525
  6. The double-strand-break repair model for recombination.
    Cell. 1983 May;33(1):25-35 PMID: 6380756
  7. Mutational analysis of the cloned chicken thymidine kinase gene.
    J Mol Appl Genet. 1983;2(2):191-200 PMID: 6875426
  8. Mitotic recombination: mismatch correction and replicational resolution of Holliday structures formed at the two strand stage in Saccharomyces.
    Mol Gen Genet. 1981;183(2):252-63 PMID: 7035826
  9. Evidence that spontaneous mitotic recombination occurs at the two-strand stage.
    Proc Natl Acad Sci U S A. 1978 Sep;75(9):4436-40 PMID: 360220
  10. Direct-repeat analysis of chromatid interactions during intrachromosomal recombination in mouse cells.
    Mol Cell Biol. 1991 Oct;11(10):4839-45 PMID: 1656213
  11. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
    Science. 1988 Jan 29;239(4839):487-91 PMID: 2448875
  12. Heteroduplex-induced mutagenesis in mammalian cells.
    Nucleic Acids Res. 1988 Mar 25;16(5):2313-22 PMID: 2833731
  13. One role for DNA methylation in vertebrate cells is strand discrimination in mismatch repair.
    Proc Natl Acad Sci U S A. 1985 Nov;82(21):7350-4 PMID: 2997788
  14. Mitotic sectored colonies: evidence of heteroduplex DNA formation during direct repeat recombination.
    Proc Natl Acad Sci U S A. 1988 Apr;85(8):2696-700 PMID: 3282237
  15. Conservative intrachromosomal recombination between inverted repeats in mouse cells: association between reciprocal exchange and gene conversion.
    Genetics. 1988 May;119(1):161-9 PMID: 3396860
  16. Repair of single-stranded DNA nicks, gaps, and loops in mammalian cells.
    Mol Cell Biol. 1987 May;7(5):1656-62 PMID: 3474515
  17. Mismatch-specific post-meiotic segregation frequency in yeast suggests a heteroduplex recombination intermediate.
    Nature. 1985 May 23-29;315(6017):350-2 PMID: 3889658
  18. The relation of mitotic recombination to DNA replication in yeast pedigrees.
    Genetics. 1970 Oct;66(2):291-304 PMID: 5512363
  19. High efficiency transformation by direct microinjection of DNA into cultured mammalian cells.
    Cell. 1980 Nov;22(2 Pt 2):479-88 PMID: 6256082
  20. Coincident gene conversion during mitosis in saccharomyces.
    Genetics. 1984 Jul;107(3):355-65 PMID: 6376279
  21. Homologous recombination between repeated chromosomal sequences in mouse cells.
    Cold Spring Harb Symp Quant Biol. 1984;49:183-9 PMID: 6597756
  22. Molecular recombination and the repair of DNA double-strand breaks in CHO cells.
    Nucleic Acids Res. 1979 Jul 11;6(9):3145-60 PMID: 493136
  23. Evidence for the formation of hybrid DNA during mitotic recombination in Chinese hamster cells.
    Cell. 1976 Aug;8(4):573-9 PMID: 954106
  24. A general model for genetic recombination.
    Proc Natl Acad Sci U S A. 1975 Jan;72(1):358-61 PMID: 1054510
  25. Genetic evidence for preferential strand transfer during meiotic recombination in yeast.
    Genetics. 1990 Aug;125(4):753-61 PMID: 2204581
  26. Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast.
    Nature. 1989 Jul 27;340(6231):318-20 PMID: 2546083
  27. Effect of the molecular nature of mutation on the efficiency of intrachromosomal gene conversion in mouse cells.
    Genetics. 1987 Dec;117(4):759-69 PMID: 2828159
  28. Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells.
    Cell. 1988 Aug 26;54(5):705-11 PMID: 2842064
  29. DNA mismatch repair detected in human cell extracts.
    Mol Cell Biol. 1987 Jan;7(1):218-24 PMID: 3031461
  30. A DNA sequence conferring high postmeiotic segregation frequency to heterozygous deletions in Saccharomyces cerevisiae is related to sequences associated with eucaryotic recombination hotspots.
    Mol Cell Biol. 1988 Mar;8(3):1253-8 PMID: 3285179
  31. The role of heteroduplex correction in gene conversion in Saccharomyces cerevisiae.
    Nature. 1987 Jul 23-29;328(6128):362-4 PMID: 3299108
  32. Repair of single-stranded loops in heteroduplex DNA transfected into mammalian cells.
    Proc Natl Acad Sci U S A. 1987 Mar;84(6):1619-23 PMID: 3470747
  33. Efficient correction of mismatched bases in plasmid heteroduplexes injected into cultured mammalian cell nuclei.
    Mol Cell Biol. 1985 Jan;5(1):70-4 PMID: 3982420
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.4.1546-1552.1992
Published
1992-04-00
Pages
1546-52
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC369596
Subset
IM
Grants
NIGMS NIH HHS · GM32741-08 · United States
NIGMS NIH HHS · GM45413-01 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.4.1546-1552.1992 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2