Telomeres shield the natural ends of chromosomes from nucleolytic attack, recognition as double-strand breaks, and inappropriate processing by DNA repair machinery. The trimeric Stn1/Ten1/Cdc13 complex is critical for chromosome end protection in Saccharomyces cerevisiae, while vertebrate telomeres are protected by shelterin, a complex of six proteins that does not include STN1 or TEN1. Recent studies demonstrate that Stn1 and Ten1 orthologs in Schizosaccharomyces pombe contribute to telomere integrity in a complex that is distinct from the shelterin components, Pot1 and Tpp1. Thus, chromosome-end protection may be mediated by distinct subcomplexes of telomere proteins. Here we report the identification of a STN1 gene in Arabidopsis that is essential for chromosome-end protection. AtSTN1 encodes an 18-kDa protein bearing a single oligonucleotide/oligosaccharide binding fold with significant sequence similarity to the yeast Stn1 proteins. Plants null for AtSTN1 display an immediate onset of growth and developmental defects and reduced fertility. These outward phenotypes are accompanied by catastrophic loss of telomeric and subtelomeric DNA, high levels of end-to-end chromosome fusions, increased G-overhang signals, and elevated telomere recombination. Thus, AtSTN1 is a crucial component of the protective telomere cap in Arabidopsis, and likely in other multicellular eukaryotes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2604966 | PMC |
| http://dx.doi.org/10.1073/pnas.0807867105 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dysfunction of Telomeric Cdc13-Stn1-Ten1 Simultaneously Activates DNA Damage and Spindle Checkpoints.
Cells
September 2024
GReD Institute, CNRS UMR6293, INSERM U1103, Faculty of Medicine, University Clermont-Auvergne, 28 Place Henri Dunant, BP 38, 63001 Clermont-Ferrand Cedex, France.
Telomeres, the ends of eukaryotic linear chromosomes, are composed of repeated DNA sequences and specialized proteins, with the conserved telomeric Cdc13/CTC1-Stn1-Ten1 (CST) complex providing chromosome stability via telomere end protection and the regulation of telomerase accessibility. In this study, , coding for a SUMO E3 ligase, and (a SUMO target for Siz1 and Siz2) were isolated as extragenic suppressors of CST temperature-sensitive mutants. -, - and - mutants were isolated next due to being sensitive to intracellular Siz1 dosage.
View Article and Find Full Text PDFShieldin and CST co-orchestrate DNA polymerase-dependent tailed-end joining reactions independently of 53BP1-governed repair pathway choice.
Nat Struct Mol Biol
September 2024
Genome Integrity laboratory, Medical Research Council Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Tumor suppressor p53-binding protein 1 (53BP1) regulates DNA end joining in lymphocytes, diversifying immune antigen receptors. This involves nucleosome-bound 53BP1 at DNA double-stranded breaks (DSBs) recruiting Rap1-interacting factor 1 homolog (RIF1) and shieldin, a poorly understood DNA-binding complex. The 53BP1-RIF1-shieldin axis is pathological in BRCA1-mutated cancers, blocking homologous recombination (HR) and driving illegitimate nonhomologous end joining (NHEJ).
View Article and Find Full Text PDFThe evolving genetic landscape of telomere biology disorder dyskeratosis congenita.
EMBO Mol Med
October 2024
Centre for Genomics and Child Health, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, Newark Street, London, E12AT, UK.
Article Synopsis
- - Dyskeratosis congenita (DC) is a rare inherited condition that leads to bone marrow failure and is largely linked to mutations affecting telomere biology, with about 35% of cases having unidentified genetic causes.
- - Research on a wide range of DC and 'DC-like' cases uncovered new pathogenic variants, including findings in the novel X-linked gene POLA1 and in known genes POT1 and ZCCHC8, enhancing the understanding of the genetic basis of these disorders.
- - Functional studies indicated that the new variants in POLA1 and POT1 disrupt crucial protein interactions that are essential for telomere maintenance, while ZCCHC8 variants lead to inflammation in patients, thereby contributing to the understanding of
Telomere C-Strand Fill-In Machinery: New Insights into the Human CST-DNA Polymerase Alpha-Primase Structures and Functions.
Subcell Biochem
July 2024
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Telomeres at the end of eukaryotic chromosomes are extended by a specialized set of enzymes and telomere-associated proteins, collectively termed here the telomere "replisome." The telomere replisome acts on a unique replicon at each chromosomal end of the telomeres, the 3' DNA overhang. This telomere replication process is distinct from the replisome mechanism deployed to duplicate the human genome.
View Article and Find Full Text PDFHuman CST Stimulates Base Excision Repair to Prevent the Accumulation of Oxidative DNA Damage.
J Mol Biol
August 2024
Department of Biological Sciences, University of South Carolina, Columbia, USA; Department of Biology, Western Kentucky University, Bowling Green, KY, USA. Electronic address:
CTC1-STN1-TEN1 (CST) is a single-stranded DNA binding protein vital for telomere length maintenance with additional genome-wide roles in DNA replication and repair. While CST was previously shown to function in double-strand break repair and promote replication restart, it is currently unclear whether it has specialized roles in other DNA repair pathways. Proper and efficient repair of DNA is critical to protecting genome integrity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!