This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yang, D.
Right arrow Articles by Waldman, A. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, D.
Right arrow Articles by Waldman, A. S.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 07 1997, 3614-3628, Vol 17, No. 7
Copyright © 1997, American Society for Microbiology

Fine-resolution analysis of products of intrachromosomal homeologous recombination in mammalian cells

D Yang and AS Waldman
Department of Biological Sciences, University of South Carolina, Columbia 29208, USA.

Mouse Ltk- cell lines that contained a herpes simplex virus type 1 (HSV- 1) thymidine kinase (tk) gene with a 16-bp insertion mutation linked to either a defective HSV-2 tk gene or a hybrid tk sequence comprised of HSV-1 and HSV-2 tk sequences were constructed. HSV-1 and HSV-2 tk genes have 81% nucleotide identity and hence are homeologous. Correction of the insertion mutant HSV-1 tk gene via recombination with the hybrid tk sequence required an exchange between homeologous tk sequences, although recombination could initiate within a region of significant sequence identity. Seven cell lines containing linked HSV-1 and HSV-1- HSV-2 hybrid tk sequences gave rise to tk+ segregants at an average rate of 10(-8) events per cell division. DNA sequencing revealed that each recombinant from these lines displayed an apparent gene conversion which involved an accurate transfer of an uninterrupted block of information between homeologous tk sequences. Conversion tract lengths ranged from 35 to >330 bp. In contrast, cell lines containing linked HSV-1 and HSV-2 tk sequences with no significant stretches of sequence identity had an overall rate of homeologous recombination of <10(-9). One such cell line produced homeologous recombinants at a rate of 10(- 8). Strikingly, all homeologous recombinants from this latter cell line were due to crossovers between the HSV-1 and HSV-2 tk genes. Our results, which provide the first detailed analysis of homeologous recombination within a mammalian genome, suggest that rearrangements in mammalian genomes are regulated by the degree of sequence divergence located at the site of recombination initiation.


This article has been cited by other articles:

  • Smith, J. A., Bannister, L. A., Bhattacharjee, V., Wang, Y., Waldman, B. C., Waldman, A. S. (2007). Accurate Homologous Recombination Is a Prominent Double-Strand Break Repair Pathway in Mammalian Chromosomes and Is Modulated by Mismatch Repair Protein Msh2. Mol. Cell. Biol. 27: 7816-7827 [Abstract] [Full Text]  
  • Yang, D., Goldsmith, E. B., Lin, Y., Waldman, B. C., Kaza, V., Waldman, A. S. (2006). Genetic Exchange Between Homeologous Sequences in Mammalian Chromosomes Is Averted by Local Homology Requirements for Initiation and Resolution of Recombination. Genetics 174: 135-144 [Abstract] [Full Text]  
  • Schildkraut, E., Miller, C. A., Nickoloff, J. A. (2006). Transcription of a Donor Enhances Its Use during Double-Strand Break-Induced Gene Conversion in Human Cells. Mol. Cell. Biol. 26: 3098-3105 [Abstract] [Full Text]  
  • D'Anjou, H., Chabot, C., Chartrand, P. (2004). Preferential accessibility to specific genomic loci for the repair of double-strand breaks in human cells. Nucleic Acids Res 32: 6136-6143 [Abstract] [Full Text]  
  • Gogarten, J. P., Doolittle, W. F., Lawrence, J. G. (2002). Prokaryotic Evolution in Light of Gene Transfer. Mol Biol Evol 19: 2226-2238 [Abstract] [Full Text]  
  • Allen, C., Kurimasa, A., Brenneman, M. A., Chen, D. J., Nickoloff, J. A. (2002). DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination. Proc. Natl. Acad. Sci. USA 99: 3758-3763 [Abstract] [Full Text]  
  • Quintana, P. J. E., Neuwirth, E. A. H., Grosovsky, A. J. (2001). Interchromosomal Gene Conversion at an Endogenous Human Cell Locus. Genetics 158: 757-767 [Abstract] [Full Text]  
  • Lin, Y., Lukacsovich, T., Waldman, A. S. (1999). Multiple Pathways for Repair of DNA Double-Strand Breaks in Mammalian Chromosomes. Mol. Cell. Biol. 19: 8353-8360 [Abstract] [Full Text]  
  • Waldman, A. S., Tran, H., Goldsmith, E. C., Resnick, M. A. (1999). Long Inverted Repeats Are an At-Risk Motif for Recombination in Mammalian Cells. Genetics 153: 1873-1883 [Abstract] [Full Text]  
  • Nickoloff, J. A., Sweetser, D. B., Clikeman, J. A., Khalsa, G. J., Wheeler, S. L. (1999). Multiple Heterologies Increase Mitotic Double-Strand Break-Induced Allelic Gene Conversion Tract Lengths in Yeast. Genetics 153: 665-679 [Abstract] [Full Text]  
  • Kavanagh, T. A., Thanh, N. D., Lao, N. T., McGrath, N., Peter, S. O., Horváth, E. M., Dix, P. J., Medgyesy, P. (1999). Homeologous Plastid DNA Transformation in Tobacco Is Mediated by Multiple Recombination Events. Genetics 152: 1111-1122 [Abstract] [Full Text]  
  • Lukacsovich, T., Waldman, A. S. (1999). Suppression of Intrachromosomal Gene Conversion in Mammalian Cells by Small Degrees of Sequence Divergence. Genetics 151: 1559-1568 [Abstract] [Full Text]  
  • Chen, W., Jinks-Robertson, S. (1998). Mismatch Repair Proteins Regulate Heteroduplex Formation during Mitotic Recombination in Yeast. Mol. Cell. Biol. 18: 6525-6537 [Abstract] [Full Text]  
  • Fabisiewicz, A., Worth, L. Jr. (2001). Escherichia coli MutS,L Modulate RuvAB-dependent Branch Migration between Diverged DNA. J. Biol. Chem. 276: 9413-9420 [Abstract] [Full Text]