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Baumann Lab demonstrates role of protein in distinguishing chromosome ends from DNA breaks
September 18, 2009The Stowers Institute's Baumann Lab has demonstrated how human cells protect chromosome ends from misguided repairs that can lead to cancer. The work, published in The EMBO Journal, a publication of the European Molecular Biology Organization, follows the team's 2007 in vitro demonstration of the role of the hRAP1 protein in preventing chromosome ends from being fused to new DNA breaks.
Chromosomes are linear. Their ends (called telomeres) should look like DNA breaks to the proteins that repair them. But somehow, cells are able to distinguish chromosome ends from DNA breaks. In this work, the team demonstrated that the human RAP1 protein plays a key role in preventing chromosome ends from being fused to new DNA breaks. Chromosome end fusions result in genomic instability, which can cause cancer. These findings suggest that RAP1 plays a critical role in cancer prevention in humans.
"Protecting naturally occurring chromosome ends from erosion and fusions may increase longevity and reduce cancer risk," said Jay Sarthy, formerly a graduate student in the Baumann Lab and lead author on the paper. "A protein that protects chromosome ends may provide an attractive target for drugs that can help to stave off aging and cancer."
"Our finding has paved the way to investigate the mechanism by which hRAP1 protects chromosome ends from undergoing fusions," said Peter Baumann, Ph.D., Associate Investigator and senior author on the publication. "This research contributes to our understanding of chromosome stability and, thereby, tumor suppression and cancer. If partial loss of hRAP1 function causes chromosomal instability, as suggested by our current work, then mutations in RAP1 may be linked to a predisposition for cancer."
Identifying hRAP1 as a critical protector of chromosome ends was an important step in understanding how telomeres are protected from DNA repair. The Baumann Lab will move forward in their efforts to understand what hRAP1 does to protect telomeres from repair - the proteins with which it interacts, and how it inactivates DNA repair specifically at chromosome ends.
Stowers Institute for Medical Research
"Our finding has paved the way to investigate the mechanism by which hRAP1 protects chromosome ends from undergoing fusions," said Peter Baumann, Ph.D., Associate Investigator and senior author on the publication. "This research contributes to our understanding of chromosome stability and, thereby, tumor suppression and cancer. If partial loss of hRAP1 function causes chromosomal instability, as suggested by our current work, then mutations in RAP1 may be linked to a predisposition for cancer."
Identifying hRAP1 as a critical protector of chromosome ends was an important step in understanding how telomeres are protected from DNA repair. The Baumann Lab will move forward in their efforts to understand what hRAP1 does to protect telomeres from repair - the proteins with which it interacts, and how it inactivates DNA repair specifically at chromosome ends.
Stowers Institute for Medical Research
Chromosome Ends Current Events and Chromosome Ends News RSSProtein plays unexpected role protecting chromosome tips
A protein specialist that opens the genomic door for DNA repair and gene expression also turns out to be a multi-tasking workhorse that protects the tips of chromosomes and dabbles in a protein-destruction complex, a team lead by researchers at The University of Texas M. D. Anderson Cancer Center reports in the Aug. 13 edition of Molecular Cell.
Handle with care: Telomeres resemble DNA fragile sites
Telomeres, the repetitive sequences of DNA at the ends of linear chromosomes, have an important function: They protect vulnerable chromosome ends from molecular attack.
Baumann lab identifies elusive telomere RNA subunit in single cell model
The Stowers Institute's Baumann Lab has identified the long-sought telomerase RNA gene in a single-cell research model. Their findings have been posted to the Web site of the journal Nature Structural & Molecular Biology and will appear in a future print edition.
Protein 'chatter' linked to cancer activation
Scientists have found the existence of cross-talk between human chromosome ends and the protein complexes central to the stability of the entire human genome, a "chat" that contributes to cancer development.
Baumann Lab Defines Proteins that Distinguish Chromosome Ends from DNA Double-Strand Breaks
Peter Baumann, Ph.D., Assistant Investigator, and Nancy Bae, Ph.D., Postdoctoral Research Associate in the Baumann Lab, have published a paper offering insight into the way cells protect chromosome ends from misguided repair.
New genetic biomarkers could predict coronary heart disease
New genetic markers may be able to predict whether a person is likely to have coronary heart disease (CAD) in the future. Research carried out by Dr. M. Balasubramanyam and Dr.V.Mohan at the Madras Diabetes Research Foundation (India) shows that people who are pre-diabetic or who have Type 2 diabetes have much shorter telomeres1 and, since these people are prone to CAD, an early test could indicate their susceptibility and help them to alter their lifestyle to avoid or delay the onset of the disease.
Gene mutations linked to hereditary lung disease
Scientists at Johns Hopkins have identified the genetic culprits that trigger a hereditary form of a fatal lung disease. The findings, published in the March 29, 2007 issue of the New England Journal of Medicine, may provide new directions in diagnosis and treatment for families that inherit genes for the disease, as well as for those that develop non-inherited forms of the illness.
DNA repair teams' motto: 'To protect and serve'
When you dial 911 you expect rescuers to pull up at your front door, unload and get busy-not park the truck down the street and eat donuts.
Evidence of rapid evolution is found at the tips of chromosomes
In terms of their telomeres, mice are more complicated than humans. That's the finding from a recent Rockefeller University study, which shows that mice have two proteins working together to do the job of a single protein in human cells.
RNAi and telomere length
A team of Russian scientists, led by Dr. Vladimir Gvozdev (Russian Academy of Sciences) reports on a novel link between RNAi and telomere maintenance in the Drosophila germline.
More Chromosome Ends Current Events and Chromosome Ends News Articles
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Cell: Volume 97 Number 4 May 14, 1999; Telomere Loop Seals Chromosome End by Cell Press (Publisher) | |
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Coming to a bad end: lost chromosome tips linked to heart problems.(This Week): An article from: Science News by N. Seppa (Author) This digital document is an article from Science News, published by Thomson Gale on January 20, 2007. The length of the article is 513 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Coming to a bad end: lost chromosome tips linked to heart problems.(This Week) Author: N. Seppa Publication: Science News (Magazine/Journal) Date: January 20, 2007 Publisher: Thomson Gale Volume: 171 Issue: 3 Page: 36(2) Distributed by Thomson... | |
![Molecular processes of chromosome 9p21 deletions causing inactivation of the p16 tumor suppressor gene in human cancer: Deduction from structural analysis ... for deletions [An article from: DNA Repair]](http://ecx.images-amazon.com/images/I/51FZ3K9Y7XL._SL160_.jpg) |
Molecular processes of chromosome 9p21 deletions causing inactivation of the p16 tumor suppressor gene in human cancer: Deduction from structural analysis ... for deletions [An article from: DNA Repair] by T. Kohno (Author), J. Yokota (Author) This digital document is a journal article from DNA Repair, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: Chromosome interstitial deletion (i.e., deletion of a chromosome segment in a chromosome arm) is a critical genetic event for the inactivation of tumor suppressor genes and activation of oncogenes leading to the carcinogenic conversion of human cells. The deletion at chromosome 9p21 removing the p16 tumor suppressor gene is a genetic alteration frequently observed in a variety of human cancers. Thus, structural analyses of breakpoints for p16 deletions in several kinds of human cancers have been performed to elucidate the... |
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DNA double-strand break repair and chromosome translocations [An article from: DNA Repair] by S. Agarwal (Author), A.A. Tafel (Author), R. Kanaar (Author) This digital document is a journal article from DNA Repair, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: Translocations are genetic aberrations that occur when a broken fragment of a chromosome is erroneously rejoined to another chromosome. The initial event in the creation of a translocation is the formation of a DNA double-strand break (DSB), which can be induced both under physiological situations, such as during the development of the immune system, or by exogenous DNA damaging agents. Two major repair pathways exist in cells that repair DSBs as they arise, namely homologous recombination, and non-homologous end-joining.... |
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Modulation of error-prone double-strand break repair in mammalian chromosomes by DNA mismatch repair protein Mlh1 [An article from: DNA Repair] by L.A. Bannister (Author), B.C. Waldman (Author), A.S. Waldman (Author) This digital document is a journal article from DNA Repair, published by Elsevier in 2004. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: We assayed error-prone double-strand break (DSB) repair in wild-type and isogenic Mlh1-null mouse embryonic fibroblasts containing a stably integrated DSB repair substrate. The substrate contained a thymidine kinase (tk) gene fused to a neomycin-resistance (neo) gene; the tk-neo fusion gene was disrupted in the tk portion by a 22bp oligonucleotide containing the 18bp recognition site for endonuclease I-SceI. Following DSB-induction by transient expression of I-SceI endonuclease, cells that repaired the DSB by error-prone... |
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The involvement of key DNA repair pathways in the formation of chromosome rearrangements in embryonic stem cells [An article from: DNA Repair] by C. Griffin (Author), H.d. Waard (Author), B. Deans (Author), J. Thacker (Author) This digital document is a journal article from DNA Repair, published by Elsevier in . The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser. Description: It is vital that embryonic stem (ES) cells, which give rise to the diverse tissues of the mature organism, maintain genetic stability. To understand mechanisms for the prevention and causation of chromosomal instability, we have used spectral karyotyping (SKY) to analyse ES cells from wild-type and repair-gene knockout mice. We chose cells deficient in Ku70 (DNA end joining), Xrcc2 (gene conversion), Ercc1 (single-strand annealing) and Csb (transcription-coupled repair) to represent potentially-important DNA repair pathways,... |
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The fusion of broken ends of sister half-chromatids following chromatid breakage at meiotic anaphases (Research bulletin / University of Missouri, Agricultural Experiment Station) by Barbara McClintock (Author) |
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