Bibliographic record
Abstract
The 2009 Nobel Prize in Physiology or Medicine was awarded to Drs Blackburn, Szostak and Greider for their discovery of how chromosomes are protected by telomeres and the enzyme telomerase. This minireview series consisting of three independent reviews discusses different aspects of this research, an area fuelling clinical applications in various human diseases including ageing and cancer. The Nobel Prize in Physiology or Medicine 2009 was jointly awarded to Drs Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak in recognition of their cutting-edge discoveries about how the chromosomes are protected by telomeres and the enzyme telomerase. Telomeres and telomerase are essential for preserving genome integrity and stability. Telomeres are repetitive DNA sequences at the ends of linear chromosomes and telomerase is the enzyme (a reverse transcriptase) responsible for their synthesis and elongation. Degradation of chromosomal ends without sufficient telomeres is detrimental and represents the underlying mechanism behind various human diseases, including ageing and cancer. As a result, research on telomeres and telomerase has increased dramatically over recent decades, with an upsurge of interest in unravelling the functions of telomeres and telomerase. This minireview series aims to summarize current knowledge of telomere biology. The three independent articles cover different facets of telomere research, from telomere medical biology and the implications for human diseases, to biogenesis and regulation of the telomerase holoenzyme complex, and to the roles of telomerase in cancer progression. The first minireview by Kong and colleagues focuses on the role of telomeres and telomere-associated proteins in the pathogenesis of human diseases, emphasizing the importance of proper telomere maintenance. Accumulating experimental data support the idea that telomeres are causally linked to various human genetic and metabolic diseases, as well as to cancer. The last few decades have witnessed remarkable advances in our understanding of this association at the molecular level. The minireview discusses the evidence that links telomere dysfunction to the diseases, as well as how defects in telomere maintenance contribute to disease manifestation. Our understanding of the human telomerase holoenzyme complex has vastly improved subsequent to its discovery by Blackburn and Greider in 1985. In the second minireview, Hukezalie and Wong focus on the biogenesis and regulation of this enzyme complex. After description of the structures of the human telomerase reverse transcriptase component (TERT) and telomerase RNA component (TER), the intricate structure–activity relationship of TERT and TER is discussed. The dynamic cellular pathways for the biogenesis and regulation of the telomerase holoenzyme, and the synthesis of telomerase-mediated telomeric repeats, are also covered. As a result of many years of intensive research, it has become more apparent that the activation of telomerase is a major step in the progression of human cancers. Telomeres normally shorten with each cell division in the absence of telomerase, although cancerous cells are able to avoid this fate and extend their survival. In the third minireview, Ding and colleagues focus on the role of telomerase activation in cancer progression, highlighting the telomere-independent mechanisms of telomerase in several essential cellular functions. These include the regulation of gene expression, mitochondrial function, cell survival and transformation, as well as the epithelial–mesenchymal transition of human cells. This minireview series provides an overview of current and future prospects of telomere biology that will be of considerable interest to both scientists and clinicians. Building on our understanding of telomere biology, scientists and clinicians are continually seeking new ways of using telomeres and telomerase as potential diagnostic and therapeutic tools. Xueying Wang was awarded a specialist degree in biochemistry from the University of Toronto, supported by the Economic Developmental Board of Singapore and Glaxo Wellcome. After obtaining her PhD in 2006, she joined Professor Elizabeth Blackburn's laboratory where she held a Susan Komen Breast Cancer Foundation fellowship. Dr X. Wang has won many awards, including the AACR-MERCK award, and was appointed the Principal Investigator in the National University of Singapore in 2008 to further research on telomeres and telomerase in human genome integrity protection for the treatment of cancer and ageing disorders.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".