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Related Concept Videos

RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...

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Related Experiment Video

Updated: Jul 4, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

ATR regulates fragile site stability.

Anne M Casper1, Paul Nghiem, Martin F Arlt

  • 1Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.

Cell
|January 16, 2003
PubMed
Summary

Common fragile sites, prone to breaks in tumors, are stabilized by the ATR kinase. ATR deficiency causes fragile site expression, revealing their role in unreplicated DNA regions and stalled replication forks.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Biology

Background:

  • Common fragile sites (CFS) are chromosomal regions susceptible to gaps and breaks under replication stress.
  • CFS instability, including deletions and rearrangements, is frequently observed in various human tumors.
  • The precise molecular mechanisms underlying CFS expression and their link to genomic instability in cancer remain largely unknown.

Purpose of the Study:

  • To elucidate the role of replication checkpoint kinases, specifically ATR and ATM, in the maintenance of fragile site stability.
  • To investigate whether ATR or ATM is essential for preventing fragile site expression during DNA replication stress.
  • To propose a model for fragile site formation based on the function of the ATR replication checkpoint.

Main Methods:

More Related Videos

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
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A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene

Published on: September 16, 2019

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP
09:46

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP

Published on: January 24, 2025

Related Experiment Videos

Last Updated: Jul 4, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
08:22

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene

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Capturing Common Fragile Site Breaks by Native γH2A.X ChIP
09:46

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP

Published on: January 24, 2025

  • Utilizing cell-based assays to assess fragile site expression under conditions of partial DNA replication inhibition.
  • Employing genetic approaches to deplete or inactivate ATR and ATM kinases in mammalian cells.
  • Analyzing metaphase chromosomes for the presence of gaps, breaks, and rearrangements indicative of fragile site expression.

Main Results:

  • The study demonstrates that the ATR kinase, but not ATM, is crucial for maintaining the stability of common fragile sites.
  • ATR deficiency leads to the characteristic expression of fragile sites, even in the absence of external replication inhibitors.
  • These findings indicate that fragile sites represent unreplicated chromosomal segments where replication forks have escaped ATR-mediated checkpoint control.

Conclusions:

  • Fragile site instability is critically dependent on the ATR-mediated replication checkpoint.
  • ATR deficiency results in the spontaneous expression of fragile sites, suggesting they are inherently unstable regions prone to stalling.
  • The proposed model posits that fragile sites are unreplicated regions arising from stalled replication forks that evade ATR surveillance, with significant implications for cancer development and genome stability.