Yeast Artificial Chromosomes

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A YAC ( Yeast Artificial Chromosome ) is an artificial chromosome that is modeled on the chromosomes of yeast .

properties

It serves as a vector and, in contrast to the cosmids, allows larger genome segments to be cloned . The first YAC was created as a combination of an ARS and a centromere of yeast with the telomeres of Tetrahymena , creating a linear molecule that behaves like a normal chromosome in yeast. The first YAC was developed by Murray and Szostak in 1983.

Despite this advantage, the YACs have a major disadvantage. Because of their length, it is very difficult to handle and keep intact in a liquid medium. For this reason one tried earlier not to construct the sections longer than 50-100 kbp . Short DNA fragments were removed from the molecule by fractionation by pulsed field gel electrophoresis and the average length could be increased to 350 kbp. The use of polyamines enabled the molecules to be stabilized, which enabled insertions of up to 700 kbp for use in the human and mouse genome . In 1992 a gene library with average insertion sizes of 810 kbp was developed, with some molecules reaching lengths of up to 1800 kbp.

As alternatives to the YACs, BACs and PACs , and finally even MACs (big MACs) and Human Artificial Chromosomes have been developed.

Individual evidence

  1. ^ AW Murray and JW Szostak : Construction of artificial chromosomes in yeast. In: Nature. Volume 305, 1983, pp. 2049-2054
  2. ^ R. Anand, A. Villasante, C. Tyler-Smith: Construction of yeast artificial chromosome libraries with large inserts using fractionation by pulsed-field gel electrophoresis. In: Nucleic Acids Res. (1989), Vol. 17 (9), pp. 3425-33. PMID 2542900 ; PMC 317785 (free full text).
  3. ↑ Z. Larin, AP Monaco, H. Lehrach : Yeast artificial chromosome libraries containing large inserts from mouse and human DNA. In: Proc Natl Acad Sci U.S.A. (1991), Vol. 88 (10), pp. 4123-7. PMID 2034658 ; PMC 51610 (free full text).
  4. ↑ C. Bellanné-Chantelot, B. Lacroix, P. Ougen, A. Billault, S. Beaufils, S. Bertrand, I. Georges, F. Glibert, I. Gros, G. Lucotte, et al .: Mapping the whole human genome by fingerprinting yeast artificial chromosomes. In: Cell (1992), vol. 70 (6), pp. 1059-68. PMID 1525822 .
  5. ↑ K. Narayanan, Q. Chen: Bacterial artificial chromosome mutagenesis using recombineering. In: J Biomed Biotechnol. (2011), p. 971296. doi: 10.1155 / 2011/971296 . PMID 21197472 ; PMC 3005948 (free full text).
  6. ^ ML Kennard: Engineered mammalian chromosomes in cellular protein production: future prospects. In: Methods Mol Biol. (2011), Volume 738, pp. 217-38. doi : 10.1007 / 978-1-61779-099-7_15 . PMID 21431730 .
  7. ↑ RL Katona, SL Vanderbyl, CF Perez: Mammalian artificial chromosomes and clinical applications for genetic modification of stem cells: an overview. In: Methods Mol Biol. (2011), Volume 738, pp. 199-216. doi : 10.1007 / 978-1-61779-099-7_14 . PMID 21431729 .
  8. ^ JH Bergmann, NM Martins, V. Larionov, H. Masumoto, WC Earnshaw: HACking the centromere chromatin code: insights from human artificial chromosomes. In: Chromosome Res. (2012), Volume 20 (5), pp. 505-19. doi: 10.1007 / s10577-012-9293-0 . PMID 22825423 .