In many organisms, telomeric DNA consists of long tracts of short repeats. Shorter tracts are preferentially lengthened by telomerase, suggesting a conserved mechanism that recognizes and elongates short telomeres. Tel1p, an ATM family checkpoint kinase, plays an important role in telomere elongation, as cells lacking Tel1p have short telomeres and show reduced recruitment of telomerase components to telomeres. We show that Tel1p association increased as telomeres shortened in vivo in the presence or absence of telomerase and that Tel1p preferentially associated with the shortest telomeres. Tel1p association was independent of Tel1p kinase activity and enhanced by Mre11p. Tel1p overexpression simultaneously stimulated telomerase-mediated elongation and Tel1p association with all telomeres. Thus, Tel1p preferentially associates with the shortest telomeres and stimulates their elongation by telomerase.
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Tel1 is the budding yeast ortholog of the mammalian tumor suppressor and DNA damage response (DDR) kinase ATM. However, tel1-Δ cells, unlike ATM-deficient cells, do not exhibit sensitivity to DNA-damaging agents, but do display shortened (but stably maintained) telomere lengths. Neither the extent to which Tel1p functions in the DDR nor the mechanism by which Tel1 contributes to telomere metabolism is well understood.
View Article and Find Full Text PDFMec1p associates with functionally compromised telomeres.
Chromosoma
June 2012
Department of Molecular Genetics, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Lerner Research Institute, 9500 Euclid Avenue, NE20, Cleveland, OH 44195, USA.
In many organisms, telomere DNA consists of simple sequence repeat tracts that are required to protect the chromosome end. In the yeast Saccharomyces cerevisiae, tract maintenance requires two checkpoint kinases of the ATM family, Tel1p and Mec1p. Previous work has shown that Tel1p is recruited to functional telomeres with shorter repeat tracts to promote telomerase-mediated repeat addition, but the role of Mec1p is unknown.
View Article and Find Full Text PDFChromosome rearrangements and aneuploidy in yeast strains lacking both Tel1p and Mec1p reflect deficiencies in two different mechanisms.
Proc Natl Acad Sci U S A
June 2010
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
The human ATM and ATR proteins participate in the DNA damage and DNA replication checkpoint pathways and are critical to maintaining genome stability. The Saccharomyces cerevisiae homologs of ATM and ATR are Tel1p and Mec1p, respectively. Haploid tel1 mec1 strains have very short telomeres and very high rates of chromosomal aberrations.
View Article and Find Full Text PDFKinase-independent functions of TEL1 in telomere maintenance.
Mol Cell Biol
September 2009
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
TEL1 is important in Saccharomyces cerevisiae telomere maintenance, and its kinase activity is required. Tel1p associates with telomeres in vivo, is enriched at short telomeres, and enhances the binding of telomerase components to short telomeres. However, it is unclear how the kinase activity and telomere association contribute to Tel1p's overall function in telomere length maintenance.
View Article and Find Full Text PDFThe Mec1p and Tel1p checkpoint kinases allow humanized yeast to tolerate chronic telomere dysfunctions by suppressing telomere fusions.
DNA Repair (Amst)
February 2009
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma "La Sapienza", Roma, Italy.
In this work we report that budding yeasts carrying human-type telomeric repeats at their chromosome termini show a chronic activation of the Rad53-dependent DNA damage checkpoint pathway and a G2/M cell cycle delay. Furthermore, in the absence of either TEL1/ATM or MEC1/ATR genes, which encodes phosphatidylinositol 3-kinase-related kinases (PIKKs), we detected telomere fusions, whose appearance correlates with a reduced cell viability and a high rate of genome instability. Based on sequence analysis, telomere fusions occurred primarily between ultrashort telomeres.
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