The
 Saccharomyces CDC
 13
 protein is a single-strand TG
 1–3
 telomeric DNA-binding protein
 in vitro
 that affects telomere behavior 
 in vivo

Lin, J. G.; Zakian, Virginia A.

doi:10.1073/pnas.93.24.13760

Cited by 291 publications

(295 citation statements)

References 37 publications

Supporting

Mentioning

281

Contrasting

Order By: Relevance

“…It is possible that Cdc13 binds to the region containing a 10-base pair single-stranded TG-like repeat (AACCACACCA), sequence that locates 5 kb from the HO cleavage site. Cdc13 shows some affinity to 10 nucleotides of embedded TG sequence in vitro (Lin and Zakian, 1996;Hughes et al, 2000). Alternatively, Cdc13 might interact weakly with more diverged sequences at other locations.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Alternatively, Cdc13 might interact weakly with more diverged sequences at other locations. Cdc13 has been shown to bind to mammalian telomeric T 2 AG 3 repeat sequences in vivo and in vitro (Lin and Zakian, 1996;Alexander and Zakian, 2003).The TG sequence seems to attenuate checkpoint signaling only from the adjacent DNA end. In TG-HO cells, Rad53 is phosphorylated after DSB induction but its phosphorylation tapers off at a later time point.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Hirano

Sugimoto

2007

MBoC

View full text Add to dashboard Cite

Chromosome ends, known as telomeres, have to be distinguished from DNA breaks that activate DNA damage checkpoint. Two large protein kinases, ataxia-teleangiectasia mutated (ATM) and ATM-Rad3-related (ATR), control not only checkpoint activation but also telomere length. In budding yeast, Mec1 and Tel1 correspond to ATR and ATM, respectively. Here, we show that Cdc13-dependent telomere capping attenuates Mec1 association with DNA ends. The telomeric TG repeat sequence inhibits DNA degradation and decreases Mec1 accumulation at the DNA end. The TG-mediated degradation block requires binding of multiple Cdc13 proteins. The Mre11-Rad50-Xrs2 complex and Exo1 contribute to DNA degradation at DNA ends. Although the TG sequence impedes Exo1 association with DNA ends, it allows Mre11 association. Moreover, the TG sequence does not affect Tel1 association with the DNA end. Our results suggest that the Cdc13 telomere cap coordinates Mec1 and Tel1 accumulation rather than simply covering the DNA ends at telomeres. INTRODUCTIONDNA double-strand breaks (DSBs) are induced by exogenous DNA-damaging agents and carcinogens or by endogenous by-products, including reactive oxygen species (Friedberg et al., 2006). The repair of DSBs is crucial for maintaining genome stability. All organisms respond to DSBs by promptly launching the DNA damage response. This response involves the recruitment of DNA repair factors and the activation of signal transduction pathways, often termed DNA damage checkpoint pathways (Zhou and Elledge, 2000). Activation of the checkpoint pathway induces cell cycle arrest and expression of genes required for DNA repair.The checkpoint signals are initiated through two large protein kinases, ataxia-teleangiectasia mutated (ATM) and ATM-Rad3-related (ATR) (Zhou and Elledge, 2000;Abraham, 2001). ATM and ATR are highly conserved among eukaryotes. ATR is closely related to Mec1 in the budding yeast Saccharomyces cerevisiae and Rad3 in the fission yeast Schizosaccharomyces pombe. ATM homologues are termed Tel1 in both budding and fission yeasts. Current evidence indicates that the Mre11-Rad50 -Nbs1 (Xrs2 in budding yeast) complex is the primary sensor that recruits ATR/ Mec1 and ATM/Tel1 to DSBs (Nakada et al., 2003a(Nakada et al., , 2004Falck et al., 2005;You et al., 2005). In budding yeast, there is compelling evidence that the Mre11-Rad50 -Xrs2 (MRX) complex collaborates with exonuclease 1 (Exo1) in the generation of single-stranded DNA (ssDNA) at DSB ends (Krogh and Symington, 2004). ATM/Tel1 interacts with the C terminus of Nbs1/Xrs2 to localize to DNA ends (Nakada et al., 2003a;Falck et al., 2005;You et al., 2005). Meanwhile, the ssDNA that is generated at the DSB is covered with replication protein A (RPA) (Wold, 1997;Krogh and Symington, 2004). RPA-covered DNA recruits ATR/Mec1 to a region near the DSB end (Zou and Elledge, 2003;Nakada et al., 2005). ATM and ATR activate the downstream kinases CHK1 and CHK2 with assistance of checkpoint mediators, including 53BP1, BRCA1, and MDC1 (Zhou and Elledge, 2000;Bakke...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Hirano

Sugimoto

2007

MBoC

View full text Add to dashboard Cite

show abstract

“…A family of single-strand DNA-binding proteins with binding specificity for the GT sequences at telomeres has been identified whose functions include protection of the overhang from degradation and regulation of telomerase activity (8,(23)(24)(25)(26). Members of this family include the Pot1 (protection of telomeres) proteins from S. pombe to human (24), the TEBPs (telomere end-binding proteins) from ciliates (27,28), and the Cdc13 proteins from budding yeasts (8).Cdc13 is strictly required for proper S. cerevisiae telomere function (8,29,30) and mediates the activity of two primary telomere functions: end protection and telomerase regulation. Deletion of Cdc13 is lethal due to loss of the essential end protection function.…”

mentioning

confidence: 99%

“…Cdc13 is strictly required for proper S. cerevisiae telomere function (8,29,30) and mediates the activity of two primary telomere functions: end protection and telomerase regulation. Deletion of Cdc13 is lethal due to loss of the essential end protection function.…”

mentioning

confidence: 99%

Identification of the Determinants for the Specific Recognition of Single-Strand Telomeric DNA by Cdc13

2005

View full text Add to dashboard Cite

The single-strand overhang present at all known telomeres plays a critical role in mediating both the capping and telomerase regulation functions of telomeres. The telomere end-binding proteins, Cdc13 in S. cerevisiae, Pot1 in higher eukaryotes, and TEBP in the ciliated protozoa O. nova, exhibit sequence-specific binding to their respective single-strand overhangs. S. cerevisiae telomeres are composed of a heterogeneous mixture of GT-rich telomeric sequence, unlike in higher eukaryotes which have a simple repeat that is maintained with high fidelity. In yeast, the telomeric overhang is recognized by the essential protein Cdc13, which coordinates end-capping and telomerase activities at the telomere. The Cdc13-DNA-binding domain (Cdc13-DBD) binds these telomere sequences with high affinity (3 pM) and sequence specificity. To better understand the basis for this remarkable recognition, we have investigated the binding of the Cdc13-DBD to a series of altered DNA substrates. Although an 11-mer of GT-rich sequence is required for full binding affinity, only 3 of these 11 bases are recognized with high specificity. This specificity differs from that observed in the other known telomere end-binding proteins, but is well suited to the specific role of Cdc13 at yeast telomeres. These studies expand our understanding of telomere recognition by the Cdc13-DBD and of the unique molecular recognition properties of ssDNA binding.Recognition of single-strand DNA (ssDNA) is essential for many fundamental cellular activities, including recombination, repair, replication, transcription, translation, and telomere maintenance. Structural and biochemical studies of the proteins that mediate ssDNA-binding activity have provided key insights into the mechanism of recognition. Generally, small domains containing mixed α/β topologies, such as the OB-fold and KH domain, are used for ssDNA recognition, and binding is achieved through base and backbone interactions that are completely distinct from those used in double-strand DNA recognition (1-5). In many biological contexts DNA needs to be uniformly recognized, thus it is appropriate for this recognition to be non-sequence specific. However, in a few cases, including telomere maintenance, transcription, and viral packaging, it is imperative that recognition be exquisitely sequence specific (3,(6)(7)(8).Telomeres, the DNA, RNA and protein complexes at the ends of chromosomes, play important roles in many essential cellular functions. They regulate the proliferative lifetime of the cell and protect chromosomes from degradation or end-to-end fusion, as well as participate in meiotic segregation and chromatic silencing (reviewed in (9-13)). Telomeres are critical to the maintenance of the genome and normal development. Thus, telomere malfunction can have dramatic adverse impacts on human health, leading to cancer, aging disorders and increased human mortality (14)(15)(16)(17)(18)(19). Therefore, it is essential to understand the mechanisms through which telomeres are properly maintain...

show abstract

Telomerase

Cerone¹,

Bacchetti²

2006

Encyclopedia of Molecular Cell Biology and Molecular Medicine

View full text Add to dashboard Cite

The Saccharomyces CDC 13 protein is a single-strand TG _1–3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo

Cited by 291 publications

References 37 publications

Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Identification of the Determinants for the Specific Recognition of Single-Strand Telomeric DNA by Cdc13

Telomerase

Contact Info

Product

Resources

About

The Saccharomyces CDC 13 protein is a single-strand TG 1–3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo

Cited by 291 publications

References 37 publications

Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Cdc13 Telomere Capping Decreases Mec1 Association but Does Not Affect Tel1 Association with DNA Ends

Identification of the Determinants for the Specific Recognition of Single-Strand Telomeric DNA by Cdc13

Telomerase

Contact Info

Product

Resources

About

The Saccharomyces CDC 13 protein is a single-strand TG _1–3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo