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Telomerase: A Eukaryotic DNA Polymerase Specialized in Telomeric Repeat Synthesis

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Book cover Nucleic Acid Polymerases

Part of the book series: Nucleic Acids and Molecular Biology ((NUCLEIC,volume 30))

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Abstract

Telomerase is an RNA-dependent DNA polymerase (reverse transcriptase) specialized in the synthesis of short DNA repeats onto chromosome ends, a function essential for chromosome stability and cellular immortality in eukaryotes. Unlike conventional polymerases, telomerase is a ribonucleoprotein (RNP) enzyme, minimally composed of the catalytic telomerase reverse transcriptase (TERT) and the telomerase RNA (TR) subunit. While the TERT catalytic core is well conserved and shares several motifs with conventional reverse transcriptases, the TR subunit is highly divergent and has evolved species-specific structural elements essential for telomerase RNP assembly and biogenesis. Telomerase is unique among polymerases, capable of producing a DNA product vastly longer than the RNA template. This unique polymerization reaction relies on repeatedly regenerating and reusing the short TR template during DNA synthesis, producing the characteristic repetitive telomeric DNA sequence. Processive telomeric repeat synthesis is dependent on “template translocation” for template regeneration, a complex mechanism that is only partially understood. Correspondingly, telomerase-specific domains within telomerase TERT-TR core function cooperatively with telomerase accessory proteins to coordinate template translocation during processive telomeric DNA repeat synthesis. Telomerase is thus a fascinating polymerase, singular in function and unrivaled in complexity.

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Abbreviations

CAB:

Cajal body localization

CP2:

Ciliate counterpart

CTE:

C-terminal extension

IFD:

Insertion in fingers domain

LINE-1:

Long interspersed element-1

PLE:

Penelope-like element

RID1:

RNA-interacting domain 1

RNP:

Ribonucleoprotein

RT:

Reverse transcriptase

scaRNA:

Small Cajal body RNA

snoRNA:

Small nucleolar RNA

TASC:

Telomere adaptor sub-complex

TBE:

Template boundary element

TEN:

Telomerase essential N-terminal

TERT:

Telomerase reverse transcriptase

TR:

Telomerase RNA

TRBD:

Telomerase RNA-binding domain

TWJ:

Three-way junction

VSR:

Vertebrate-specific region

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Acknowledgments

This work was supported by National Institutes of Health (NIH) Grant R01GM094450 to J.J-L.C.

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Authors and Affiliations

  1. Department of Chemistry & Biochemistry, Arizona State University, Tempe, AZ, 85287, USA

    Andrew F. Brown, Joshua D. Podlevsky & Julian J.-L. Chen

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  1. Andrew F. Brown
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Correspondence to Julian J.-L. Chen .

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Editors and Affiliations

  1. Dept. of Biochem. and Mol. Biology, The Pennsylvania State University, University Park, Pennsylvania, USA

    Katsuhiko S. Murakami

  2. Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Michael A. Trakselis

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Brown, A.F., Podlevsky, J.D., Chen, J.JL. (2014). Telomerase: A Eukaryotic DNA Polymerase Specialized in Telomeric Repeat Synthesis. In: Murakami, K., Trakselis, M. (eds) Nucleic Acid Polymerases. Nucleic Acids and Molecular Biology, vol 30. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-39796-7_9

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