Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Cell Biol. 2007 Sep;27(18):6532-45. Epub 2007 Jul 16.

Mdt1 facilitates efficient repair of blocked DNA double-strand breaks and recombinational maintenance of telomeres.

Author information

  • 1St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, VIC 3065, Australia.

Abstract

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). mdt1Delta also hypersensitizes partially recombination-defective cells to camptothecin-induced 3'-phospho-tyrosyl protein-blocked DSBs. Remarkably, whereas mdt1Delta 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, mdt1Delta 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, mdt1Delta 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.

PMID:
17636027
[PubMed - indexed for MEDLINE]
PMCID:
PMC2099617
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk