This Article
Right arrow Full Text
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 Google Scholar
Google Scholar
Right arrow Articles by Pike, B. L.
Right arrow Articles by Heierhorst, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pike, B. L.
Right arrow Articles by Heierhorst, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 2007, p. 6532-6545, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00471-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mdt1 Facilitates Efficient Repair of Blocked DNA Double-Strand Breaks and Recombinational Maintenance of Telomeres{triangledown}

Brietta L. Pike1,{dagger} and Jörg Heierhorst1,2*

St. Vincent's Institute of Medical Research,1 Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia2

Received 19 March 2007/ Returned for modification 25 April 2007/ Accepted 6 July 2007

DNA recombination plays critical roles in DNA repair and alternative telomere maintenance. Here we show that absence of the SQ/TQ cluster domain-containing protein Mdt1 (Ybl051c) renders Saccharomyces cerevisiae particularly hypersensitive to bleomycin, a drug that causes 3'-phospho-glycolate-blocked DNA double-strand breaks (DSBs). mdt1{Delta} also hypersensitizes partially recombination-defective cells to camptothecin-induced 3'-phospho-tyrosyl protein-blocked DSBs. Remarkably, whereas mdt1{Delta} cells are unable to restore broken chromosomes after bleomycin treatment, they efficiently repair "clean" endonuclease-generated DSBs. Epistasis analyses indicate that MDT1 acts in the repair of bleomycin-induced DSBs by regulating the efficiency of the homologous recombination pathway as well as telomere-related functions of the KU complex. Moreover, mdt1{Delta} leads to severe synthetic growth defects with a deletion of the recombination facilitator and telomere-positioning factor gene CTF18 already in the absence of exogenous DNA damage. Importantly, mdt1{Delta} causes a dramatic shift from the usually prevalent type II to the less-efficient type I pathway of recombinational telomere maintenance in the absence of telomerase in liquid senescence assays. As telomeres resemble protein-blocked DSBs, the results indicate that Mdt1 acts in a novel blocked-end-specific recombination pathway that is required for the efficiency of both drug-induced DSB repair and telomerase-independent telomere maintenance.

* Corresponding author. Mailing address: St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, VIC 3065, Australia. Phone: 61-3-9288-2503. Fax: 61-3-9416-2676. E-mail: jheierhorst{at}svi.edu.au

{triangledown} Published ahead of print on 16 July 2007.

{dagger} Present address: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.

Molecular and Cellular Biology, September 2007, p. 6532-6545, Vol. 27, No. 18
0270-7306/07/$08.00+0     doi:10.1128/MCB.00471-07
Copyright © 2007, 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»