Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase

Nucleic Acids Research
Olga A PetrovaVladimir I Polshakov

Abstract

The elongation of single-stranded DNA repeats at the 3'-ends of chromosomes by telomerase is a key process in maintaining genome integrity in eukaryotes. Abnormal activation of telomerase leads to uncontrolled cell division, whereas its down-regulation is attributed to ageing and several pathologies related to early cell death. Telomerase function is based on the dynamic interactions of its catalytic subunit (TERT) with nucleic acids-telomerase RNA, telomeric DNA and the DNA/RNA heteroduplex. Here, we present the crystallographic and NMR structures of the N-terminal (TEN) domain of TERT from the thermotolerant yeast Hansenula polymorpha and demonstrate the structural conservation of the core motif in evolutionarily divergent organisms. We identify the TEN residues that are involved in interactions with the telomerase RNA and in the recognition of the 'fork' at the distal end of the DNA product/RNA template heteroduplex. We propose that the TEN domain assists telomerase biological function and is involved in restricting the size of the heteroduplex during telomere repeat synthesis.

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
May 12, 2000·European Journal of Biochemistry·T Sasaki, H Fujiwara
Jul 13, 2000·Protein Science : a Publication of the Protein Society·M L TillettT J Norwood
Feb 7, 2001·Molecular and Cellular Biology·C K LaiK Collins
Oct 18, 2001·Molecular and Cellular Biology·B N ArmbrusterC M Counter
Jan 15, 2003·Biochemistry·Gerald WallweberRonald Pruzan
Feb 14, 2004·Science·Kenneth D WestoverRoger D Kornberg
Jan 1, 1996·Acta Crystallographica. Section D, Biological Crystallography·J P Abrahams, A G Leslie
Feb 26, 2005·The Journal of Biological Chemistry·Catherine M O'ConnorKathleen Collins
Mar 19, 2005·EMBO Reports·Klaus Förstemann, Joachim Lingner
May 21, 2005·The Journal of Biological Chemistry·Neal F Lue
Jul 28, 2005·Protein Science : a Publication of the Protein Society·Steven A JacobsThomas R Cech
Oct 27, 2005·Journal of the American Chemical Society·Mark V Berjanskii, David S Wishart
Feb 8, 2006·Nature Structural & Molecular Biology·Steven A JacobsThomas R Cech
Aug 25, 2006·Acta Crystallographica. Section D, Biological Crystallography·Kevin Cowtan
Feb 14, 2007·Molecular and Cellular Biology·Haley D M WyattTara L Beattie
May 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Erez RomiHaim Manor
Jun 22, 2007·Nature·Dmitry G VassylyevIrina Artsimovitch
Sep 2, 2008·Nature·Andrew J GillisEmmanuel Skordalakes
Sep 30, 2008·Fly·Mary-Lou Pardue, P Gregory DeBaryshe
Mar 27, 2009·The Journal of Biological Chemistry·Tatyana KentDmitry Temiakov
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Mar 17, 2010·Genes & Development·Arthur J ZaugThomas R Cech
Apr 2, 2010·Nature Structural & Molecular Biology·Meghan MitchellEmmanuel Skordalakes
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·Kevin Cowtan
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·George M Sheldrick
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
May 13, 2010·Nucleic Acids Research·Haley D M WyattTara L Beattie
Jul 8, 2010·Acta Crystallographica. Section D, Biological Crystallography·Pavol SkubákNavraj S Pannu
Oct 29, 2010·Nature Communications·Christoph J WienkenStefan Duhr
Nov 6, 2010·Nucleic Acids Research·Julie JurczylukTracy M Bryan
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin

❮ Previous
Next ❯

Citations

Nov 16, 2019·Cellular and Molecular Life Sciences : CMLS·Eric M SmithJayakrishnan Nandakumar
Jun 6, 2020·ELife·Matthew A SchaichBret D Freudenthal
Jun 11, 2020·Biomolecules·Maria Rubtsova, Olga Dontsova
Apr 27, 2018·Nature·Thi Hoang Duong NguyenKathleen Collins
Jul 8, 2020·Scientific Reports·Nikita M ShepelevVladimir I Polshakov
Aug 28, 2019·Cold Spring Harbor Perspectives in Biology·Yaqiang WangJuli Feigon
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yaqiang WangJuli Feigon

❮ Previous
Next ❯

Methods Mentioned

BETA
RAP
X-ray
NMR
Electrophoresis
size exclusion chromatography
PCR
protein folding

Software Mentioned

Dials
NMRPipe package
ARIA
Coot
NMRFAM
hpTEN
MOPRO
CCP4
SHELXD
- SPARKY

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.