Multiple Mechanisms Contribute to the Cell Growth Defects Imparted by Human Telomerase Insertion in Fingers Domain Mutations Associated with Premature Aging Diseases.

The Journal of Biological Chemistry
Tsz Wai ChuChantal Autexier

Abstract

Normal human stem cells rely on low levels of active telomerase to sustain their high replicative requirements. Deficiency in telomere maintenance mechanisms leads to the development of premature aging diseases, such as dyskeratosis congenita and aplastic anemia. Mutations in the unique "insertion in fingers domain" (IFD) in the human telomerase reverse transcriptase catalytic subunit (hTERT) have previously been identified and shown to be associated with dyskeratosis congenita and aplastic anemia. However, little is known about the molecular mechanisms impacted by these IFD mutations. We performed comparative functional analyses of disease-associated IFD variants at the molecular and cellular levels. We report that hTERT-P721R- and hTERT-R811C-expressing cells exhibited growth defects likely due to impaired TPP1-mediated recruitment of these variant enzymes to telomeres. We showed that activity and processivity of hTERT-T726M failed to be stimulated by TPP1-POT1 overexpression and that dGTP usage by this variant was less efficient compared with the wild-type enzyme. hTERT-P785L-expressing cells did not show growth defects, and this variant likely confers cell survival through increased DNA synthesis and robust activity stimula...Continue Reading

References

Oct 18, 2001·Molecular and Cellular Biology·B N ArmbrusterC M Counter
May 28, 2003·Nature·Diego Loayza, Titia De Lange
Apr 9, 2005·The New England Journal of Medicine·Hiroki YamaguchiNeal S Young
May 12, 2005·Blood Cells, Molecules & Diseases·Tom J VulliamyInderjeet Dokal
Oct 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mary ArmaniosCarol W Greider
Dec 2, 2005·Molecular Biology of the Cell·Beáta E JádyTamás Kiss
Dec 13, 2005·Molecular Biology of the Cell·Rebecca L TomlinsonMichael P Terns
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·T De Lange
Nov 30, 2006·Molecular and Cellular Biology·Bryan E SnowLea Harrington
Feb 7, 2008·American Journal of Human Genetics·Sharon A SavageBlanche P Alter
Jun 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tom VulliamyInderjeet Dokal
Mar 14, 2009·Blood·Blanche P AlterPhilip S Rosenberg
Dec 22, 2009·The Journal of Biological Chemistry·Aaron R Robart, Kathleen Collins
Mar 2, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Isabelle Ourliac-GarnierSophie Bombard
Mar 17, 2010·Genes & Development·Arthur J ZaugThomas R Cech
Apr 21, 2010·Molecular and Cellular Biology·Eladio AbreuMichael P Terns
Jan 6, 2011·Genes & Development·Franklin ZhongSteven E Artandi
Apr 5, 2011·Methods in Molecular Biology·Eladio AbreuMichael P Terns
Apr 5, 2011·Methods in Molecular Biology·Feng Wang, Ming Lei
Dec 14, 2011·EMBO Reports·Zeenia KaulRoger R Reddel
Dec 14, 2011·Hematology·Inderjeet Dokal
Apr 26, 2012·Pediatric Blood & Cancer·Rachel B KellerSuneet Agarwal
May 2, 2012·Molecular and Cellular Biology·J Lewis SternTracy M Bryan
Jun 16, 2012·Science·Jerry W ShayWoodring E Wright
Aug 18, 2012·Haematologica·Amanda J WalneInderjeet S Dokal
Oct 30, 2012·Nature·Jayakrishnan NandakumarThomas R Cech
Nov 28, 2012·Journal of Cell Science·Yasmin D'SouzaChantal Autexier
May 8, 2013·The FEBS Journal·Chiou Mee KongXueying Wang

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Citations

Sep 21, 2016·Genes·Deanna Elise MacNeilChantal Autexier
Mar 17, 2017·Annual Review of Biophysics·Henry ChanJuli Feigon
Nov 16, 2019·Cellular and Molecular Life Sciences : CMLS·Eric M SmithJayakrishnan Nandakumar
Dec 12, 2019·Proceedings of the National Academy of Sciences of the United States of America·Valerie M TesmerJayakrishnan Nandakumar
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yaqiang WangJuli Feigon
Nov 14, 2020·The Journal of Biological Chemistry·Sherilyn Grill, Jayakrishnan Nandakumar
Jul 22, 2017·Current Opinion in Structural Biology·Yaqiang Wang, Juli Feigon
Jan 23, 2021·The Journal of Biological Chemistry·Sherilyn Grill, Jayakrishnan Nandakumar

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