This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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
Google Scholar
Right arrow Articles by Schonbrun, M.
Right arrow Articles by Weisman, R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schonbrun, M.
Right arrow Articles by Weisman, R.

 Previous Article

Molecular and Cellular Biology, August 2009, p. 4584-4594, Vol. 29, No. 16
0270-7306/09/$08.00+0     doi:10.1128/MCB.01879-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

TOR Complex 2 Controls Gene Silencing, Telomere Length Maintenance, and Survival under DNA-Damaging Conditions{triangledown} ,{dagger}

Miriam Schonbrun,1 Dana Laor,1 Luis López-Maury,2 Jürg Bähler,2 Martin Kupiec,1 and Ronit Weisman1,3*

Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel-Aviv, Israel,1 Department of Genetics, Evolution and Environment and UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom,2 Department of Natural and Life Sciences, Open University of Israel, Raanana, Israel3

Received 11 December 2008/ Returned for modification 7 January 2009/ Accepted 10 June 2009

The Target Of Rapamycin (TOR) kinase belongs to the highly conserved eukaryotic family of phosphatidylinositol-3-kinase-related kinases (PIKKs). TOR proteins are found at the core of two distinct evolutionarily conserved complexes, TORC1 and TORC2. Disruption of TORC1 or TORC2 results in characteristically dissimilar phenotypes. TORC1 is a major cell growth regulator, while the cellular roles of TORC2 are not well understood. In the fission yeast Schizosaccharomyces pombe, Tor1 is a component of the TORC2 complex, which is particularly required during starvation and various stress conditions. Our genome-wide gene expression analysis of {Delta}tor1 mutants indicates an extensive similarity with chromatin structure mutants. Consistently, TORC2 regulates several chromatin-mediated functions, including gene silencing, telomere length maintenance, and tolerance to DNA damage. These novel cellular roles of TORC2 are rapamycin insensitive. Cells lacking Tor1 are highly sensitive to the DNA-damaging drugs hydroxyurea (HU) and methyl methanesulfonate, similar to mutants of the checkpoint kinase Rad3 (ATR). Unlike Rad3, Tor1 is not required for the cell cycle arrest in the presence of damaged DNA. Instead, Tor1 becomes essential for dephosphorylation and reactivation of the cyclin-dependent kinase Cdc2, thus allowing reentry into mitosis following recovery from DNA replication arrest. Taken together, our data highlight critical roles for TORC2 in chromatin metabolism and in promoting mitotic entry, most notably after recovery from DNA-damaging conditions. These data place TOR proteins in line with other PIKK members, such as ATM and ATR, as guardians of genome stability.

* Corresponding author. Mailing address: Dept. of Molecular Microbiology and Biotechnology, Green Building, Room 211, Tel-Aviv University, Ramat Aviv, 69978 Tel-Aviv, Israel. Phone: (972) 03-640-9208. Fax: (972) 03-640-9407. E-mail: ronitt{at}post.tau.ac.il

{triangledown} Published ahead of print on 22 June 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, August 2009, p. 4584-4594, Vol. 29, No. 16
0270-7306/09/$08.00+0     doi:10.1128/MCB.01879-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»