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MBC in Press, published online ahead of print January 12, 2005
Mol. Biol. Cell 10.1091/mbc.E04-07-0592

A more recent version of this article appeared on March 1, 2005
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Submitted on July 15, 2004
Revised on November 29, 2004
Accepted on December 21, 2004

Involvement of Sir2/4 in Silencing of DNA Breakage and Recombination on Mouse YACs during Yeast Meiosis

Yair Klieger,* Ofer Yizhar,* Drora Zenvirth,* Neta Shtepel-Milman,* Margriet Snoek,{dagger} and Giora Simchen*{ddagger}

*Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel; {dagger}Division of Molecular Genetics, Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands

Monitoring Editor: Douglas Koshland

Yeast artificial chromosomes (YACs) that contain human DNA backbone undergo DNA double strand breaks (DSBs) and recombination during yeast meiosis at rates similar to the yeast native chromosomes. Surprisingly, YACs containing DNA covering a recombination hot spot in the mouse Major Histocompatibility Complex class III region do not show meiotic DSBs and undergo meiotic recombination at reduced levels. Moreover, segregation of these YACs during meiosis is seriously compromised. In meiotic yeast cells carrying the mutations sir2 or sir4, but not sir3, these YACs show DSBs, suggesting that a unique chromatin structure of the YACs, involving Sir2 and Sir4, protects the YACs from the meiotic recombination machinery. We speculate that the paucity of DSBs and recombination events on these YACs during yeast meiosis may reflect the refractory nature of the corresponding region in the mouse genome.

{ddagger}Corresponding author. E-mail: simchen{at}vms.huji.ac.il






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