학술논문

Telomerase Mechanism of Telomere Synthesis
Document Type
article
Source
Annual Review of Biochemistry. 86(1)
Subject
Genetics
Stem Cell Research
Underpinning research
1.1 Normal biological development and functioning
Generic health relevance
Animals
Catalytic Domain
DNA Replication
DNA
Single-Stranded
Gene Expression Regulation
Humans
Microsatellite Repeats
Nucleic Acid Conformation
Oxytricha
RNA
Ribonucleoproteins
Saccharomyces cerevisiae
Telomerase
Telomere
Tetrahymena thermophila
telomere
reverse transcriptase
ribonucleoprotein biogenesis
DNA replication
Biological Sciences
Medical and Health Sciences
Biochemistry & Molecular Biology
Language
Abstract
Telomerase is the essential reverse transcriptase required for linear chromosome maintenance in most eukaryotes. Telomerase supplements the tandem array of simple-sequence repeats at chromosome ends to compensate for the DNA erosion inherent in genome replication. The template for telomerase reverse transcriptase is within the RNA subunit of the ribonucleoprotein complex, which in cells contains additional telomerase holoenzyme proteins that assemble the active ribonucleoprotein and promote its function at telomeres. Telomerase is distinct among polymerases in its reiterative reuse of an internal template. The template is precisely defined, processively copied, and regenerated by release of single-stranded product DNA. New specificities of nucleic acid handling that underlie the catalytic cycle of repeat synthesis derive from both active site specialization and new motif elaborations in protein and RNA subunits. Studies of telomerase provide unique insights into cellular requirements for genome stability, tissue renewal, and tumorigenesis as well as new perspectives on dynamic ribonucleoprotein machines.