WRN controls formation of extrachromosomal telomeric circles and is required for TRF2DeltaB-mediated telomere shortening.

Molecular and Cellular Biology
Baomin LiLucio Comai

Abstract

Telomere dysfunction has been proposed to contribute to the pathogenesis of Werner syndrome (WS), a premature-aging disorder. The WS protein WRN binds TRF2, a telomere-specific factor that protects chromosome ends. TRF2 possesses an amino-terminal domain that plays an essential role in preventing telomere shortening, as expression of TRF2(DeltaB), which lacks this domain, leads to the formation of telomeric circles, telomere shortening, and cell senescence. Our data show that the TRF2(DeltaB)-induced telomeric-loop homologous-recombination pathway requires WRN helicase. In addition, we show that WRN represses the formation of spontaneous telomeric circles, as demonstrated by the increased levels of telomeric circles observed in telomerase-positive WS fibroblasts. The mechanism of circle formation in WS cells does not involve XRCC3 function. Circle formation in WS cells is reduced by reconstitution with wild-type WRN but not mutant forms lacking either exonuclease or helicase activity, demonstrating that both enzymatic activities of WRN are required to suppress telomeric-circle formation in normal cells expressing telomerase reverse transcriptase. Thus, WRN has a key protective function at telomeres which influences telomere top...Continue Reading

References

Oct 1, 1988·Human Genetics·E GebhartJ B Jonas
Dec 8, 1995·Science·L ChongT de Lange
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
Apr 12, 1996·Science·C E YuG D Schellenberg
Nov 5, 1997·Nature Genetics·D BroccoliT de Lange
Nov 5, 1997·Nature Genetics·T BilaudE Gilson
Feb 26, 1998·Cell·B van SteenselT de Lange
Feb 26, 1999·Science·J KarlsederT de Lange
May 25, 1999·Cell·J D GriffithT de Lange
Jul 6, 2000·The Journal of Biological Chemistry·B Li, L Comai
May 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M PootP S Rabinovitch
Mar 30, 2002·Science·Jan KarlsederTitia de Lange
Apr 30, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Martin PootPeter S Rabinovitch
Aug 16, 2002·The Journal of Biological Chemistry·Patricia L OpreskoVilhelm A Bohr
May 28, 2003·Nature·Diego Loayza, Titia De Lange
Sep 6, 2003·Current Biology : CB·Hiroyuki TakaiTitia de Lange
Jul 14, 2004·The Journal of Cell Biology·Tatiana Nikitina, Christopher L Woodcock
Jun 11, 2005·Mutation Research·Ali Ozgenc, Lawrence A Loeb
Sep 17, 2005·Genes & Development·Titia de Lange

❮ Previous
Next ❯

Citations

Oct 8, 2009·Nature Structural & Molecular Biology·Lubomir TomaskaJack D Griffith
Jul 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yongbao WangEric A Hendrickson
Jul 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sandra M Indiviglio, Alison A Bertuch
Oct 9, 2009·The Journal of Biological Chemistry·Gregory SowdPatricia L Opresko
Dec 6, 2011·Nucleic Acids Research·Anaïs PouletMarie-Josèphe Giraud-Panis
Sep 20, 2012·Nucleic Acids Research·Aaron Mendez-BermudezNicola J Royle
Aug 6, 2008·Annual Review of Genetics·Wilhelm Palm, Titia de Lange
Nov 17, 2009·Journal of Cell Science·Liana Oganesian, Jan Karlseder
Oct 8, 2013·PloS One·Guangzhen JiLin Liu
Apr 9, 2014·PloS One·April Renee Sandy GochaJoanna Groden
Aug 20, 2009·Yi chuan = Hereditas·Shu-Ting JiaYing Luo
Mar 13, 2014·Annual Review of Biochemistry·Deborah L CroteauVilhelm A Bohr
Feb 7, 2009·The EMBO Journal·Anaïs PouletMarie-Josèphe Giraud-Panis
Oct 6, 2015·Cell Regeneration·Hoi-Hung CheungWai-Yee Chan
Mar 18, 2016·Human Molecular Genetics·Weiliang TangRaymond J Monnat
Mar 17, 2015·The Biochemical Journal·Furqan SamiSudha Sharma
Jan 16, 2010·DNA Repair·Marie L RossiVilhelm A Bohr
Mar 24, 2017·Nucleic Acids Research·Cody M RogersMatthew L Bochman
Nov 7, 2017·Nature Structural & Molecular Biology·Yi-An ChenLiuh-Yow Chen
Sep 29, 2012·Journal of Cellular Physiology·Edward M JohnsonJennifer Gordon
Aug 11, 2010·FEBS Letters·Marie-Josèphe Giraud-PanisEric Gilson
Feb 3, 2018·Plant Cell Reports·Xiaoyuan Xie, Dorothy E Shippen
Mar 17, 2012·Cell Cycle·Hilda A Pickett, Roger R Reddel
Jul 9, 2011·Nucleus·Raffaella Diotti, Diego Loayza
Sep 13, 2013·The Journal of Biological Chemistry·Christopher KasbekCarolyn M Price
Aug 6, 2019·Nucleic Acids Research·Susanna StroikEric A Hendrickson
Sep 20, 2018·Seminars in Immunology·Gianluca StorciMassimiliano Bonafè
Feb 28, 2009·Biochimica Et Biophysica Acta·Alejandro ChavezF Brad Johnson
Mar 17, 2009·Molecular Cell·Ofer RogJulia Promisel Cooper

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.