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Related Concept Videos

Telomeres and Telomerase02:41

Telomeres and Telomerase

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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
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Replication in Eukaryotes01:29

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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
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Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
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In vitro Reconstitution of the Active T. castaneum Telomerase
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In vitro Reconstitution of the Active T. castaneum Telomerase

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Progress in structural studies of telomerase.

Edward J Miracco1, Jiansen Jiang2, Darian D Cash1

  • 1Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, USA.

Current Opinion in Structural Biology
|February 11, 2014
PubMed
Summary
This summary is machine-generated.

Recent advances reveal the structure of telomerase (ribonucleoprotein reverse transcriptase), crucial for chromosome maintenance, aging, and cancer. New electron microscopy data illuminate the organization of its protein and RNA components.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Telomerase is a ribonucleoprotein (RNP) reverse transcriptase essential for maintaining the 3' ends of linear chromosomes.
  • It plays significant roles in cellular aging, stem cell renewal, and tumorigenesis.
  • Understanding telomerase structure is key to elucidating its function and therapeutic targeting.

Purpose of the Study:

  • To present recent breakthroughs in determining the architecture of the telomerase holoenzyme.
  • To describe the structural basis of telomerase activity.
  • To provide insights into the organization of proteins and RNA within the telomerase RNP complex.

Main Methods:

  • Electron microscopy (EM) was utilized to determine the structures of the Tetrahymena thermophila telomerase holoenzyme and a human telomerase dimer.
  • Structural analysis focused on telomerase reverse transcriptase (TERT) and telomerase RNA (TER) domains.
  • Structures of telomerase protein domains beyond TERT, and their complexes with TER or telomeric single-stranded DNA, were determined.

Main Results:

  • The first electron microscopy structures of the telomerase holoenzyme and a human telomerase dimer were reported.
  • New structures revealed details of TERT and TER domains, as well as telomerase protein domains beyond TERT.
  • Complexes of these domains with TER or telomeric single-stranded DNA were structurally characterized.

Conclusions:

  • These structural studies offer the first comprehensive view of the organization of proteins and RNA within the telomerase RNP.
  • The findings advance our understanding of the molecular mechanisms underlying telomerase function.
  • This structural information is foundational for future research into telomerase-related diseases and therapeutic development.