Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes

Molecular and Cellular Biology
Xiaobing DuF Brad Johnson

Abstract

The Werner and Bloom syndromes are caused by loss-of-function mutations in WRN and BLM, respectively, which encode the RecQ family DNA helicases WRN and BLM, respectively. Persons with Werner syndrome displays premature aging of the skin, vasculature, reproductive system, and bone, and those with Bloom syndrome display more limited features of aging, including premature menopause; both syndromes involve genome instability and increased cancer. The proteins participate in recombinational repair of stalled replication forks or DNA breaks, but the precise functions of the proteins that prevent rapid aging are unknown. Accumulating evidence points to telomeres as targets of WRN and BLM, but the importance in vivo of the proteins in telomere biology has not been tested. We show that Wrn and Blm mutations each accentuate pathology in later-generation mice lacking the telomerase RNA template Terc, including acceleration of phenotypes characteristic of latest-generation Terc mutants. Furthermore, pathology not observed in Terc mutants but similar to that observed in Werner syndrome and Bloom syndrome, such as bone loss, was observed. The pathology was accompanied by enhanced telomere dysfunction, including end-to-end chromosome fusions...Continue Reading

References

Sep 1, 1995·Experimental Cell Research·R C AllsoppC B Harley
Apr 12, 1996·Science·C E YuG D Schellenberg
Jan 1, 1996·Human Molecular Genetics·N A Ellis, J German
Jan 1, 1996·Developmental Genetics·W E WrightJ W Shay
Oct 15, 1998·Nature Genetics·S HuangJ Campisi
Dec 16, 1998·The Journal of Biological Chemistry·J C ShenL A Loeb
Nov 11, 1999·Clinical and Experimental Immunology·H KanekoN Kondo
Dec 14, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J P Liu
Apr 11, 2000·Molecular and Cellular Biology·D B LombardL Guarente
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·V YankiwskiN F Neff
Mar 7, 2001·Current Biology : CB·P HuangE J Louis
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·H Cohen, D A Sinclair
Sep 27, 2001·Cell·E H Blackburn
Sep 28, 2001·The EMBO Journal·R M StanselJ D Griffith
Jan 10, 2002·Nature·Stuart D TynerLawrence A Donehower
Feb 13, 2002·Oncogene·Osamu ImamuraTakehisa Matsumoto
Feb 14, 2002·Differentiation; Research in Biological Diversity·Nicholas R ForsythJerry W Shay
Mar 9, 2002·Biochemical and Biophysical Research Communications·Paula SteinRichard M Schultz
Aug 16, 2002·The Journal of Biological Chemistry·Patricia L OpreskoVilhelm A Bohr
Sep 18, 2002·Nucleic Acids Research·Michael D HuberNancy Maizels
Sep 21, 2002·Science·Kathleen Heppner GossJoanna Groden
Nov 22, 2002·Human Molecular Genetics·Dimitrios J StavropoulosM Stephen Meyn
Dec 17, 2002·Oncogene·Hiroaki Nakayama
Mar 1, 2003·Science·Paul HastyJan Vijg
May 22, 2003·Cancer Letters·Roger R Reddel
Jul 12, 2003·Nature Cell Biology·Simona ParrinelloJudith Campisi
Aug 30, 2003·Trends in Cell Biology·Rakesh R KhakharSusan M Gasser
Sep 6, 2003·Current Biology : CB·Hiroyuki TakaiTitia de Lange
Nov 11, 2003·Nature·Fabrizio d'Adda di FagagnaStephen P Jackson

❮ Previous
Next ❯

Citations

Jun 20, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Maria Grazia Andreassi
Aug 27, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Haitao WangRobert J Pignolo
Dec 17, 2008·Biogerontology·Dharmendra Kumar SinghVilhelm A Bohr
Feb 21, 2013·Current Osteoporosis Reports·Monique BethelMelissa A Kacena
Apr 7, 2005·Molecular Aspects of Medicine·Ken Watanabe, Akinori Hishiya
Jun 11, 2005·Mutation Research·Ali Ozgenc, Lawrence A Loeb
Jun 7, 2005·Trends in Biochemical Sciences·Peter M Lansdorp
Sep 19, 2007·Nature Chemical Biology·Maria A Blasco
Sep 3, 2008·Nature Clinical Practice. Cardiovascular Medicine·Tohru Minamino, Issei Komuro
Jul 12, 2013·Nature Reviews. Cancer·Robert M Brosh
Sep 2, 2005·Nature Reviews. Genetics·Maria A Blasco
Apr 24, 2007·Nature Reviews. Molecular Cell Biology·Brian A KudlowRaymond J Monnat
Sep 22, 2007·Nature Reviews. Molecular Cell Biology·Eric Gilson, Vincent Géli
May 17, 2012·Nature Reviews. Molecular Cell Biology·Ergün Sahin, Ronald A DePinho
Jun 27, 2006·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Felipe Sierra
Nov 17, 2007·Nucleic Acids Research·Robert M Brosh, Vilhelm A Bohr
Dec 18, 2007·Nucleic Acids Research·Johannes GrillariRegina Voglauer
Jan 13, 2010·Molecular and Cellular Biology·Saravanabhavan ThangavelAlessandro Vindigni
Dec 13, 2006·Molecular and Cellular Biology·Sudha SharmaPerry J Blackshear
Nov 17, 2005·Molecular and Cellular Biology·Anna M SzekelySherman M Weissman
Jul 22, 2006·Annual Review of Genetics·Leonard Wu, Ian D Hickson
Nov 2, 2006·Biological & Pharmaceutical Bulletin·Akari YoshimuraTakemi Enomoto
Jun 2, 2007·Biological & Pharmaceutical Bulletin·Yu Peng DongTakemi Enomoto
Dec 18, 2013·Circulation Journal : Official Journal of the Japanese Circulation Society·Takafumi IshidaYasuki Kihara
Feb 16, 2006·PLoS Genetics·Bettina MeierShawn Ahmed
Nov 30, 2007·Clinical Interventions in Aging·Yira BermudezPatricia A Kruk
Aug 20, 2009·Yi chuan = Hereditas·Shu-Ting JiaYing Luo
Apr 9, 2014·PloS One·April Renee Sandy GochaJoanna Groden
May 22, 2013·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Robert L Jilka
Mar 13, 2014·Annual Review of Biochemistry·Deborah L CroteauVilhelm A Bohr
Dec 14, 2005·Proceedings of the National Academy of Sciences of the United States of America·Izumi HorikawaJ Carl Barrett
May 12, 2011·Current Gerontology and Geriatrics Research·Michel LebelVilhelm A Bohr

❮ 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.