Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

8.5K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
8.5K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

2.4K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.4K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

5.1K
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,...
5.1K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

4.8K
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.8K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

3.0K
3.0K
Chromosome Replication02:31

Chromosome Replication

8.9K
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...
8.9K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Plasma metabolomics identifies trimethylamine n-oxide as an accelerator of gallstone disease accompanied by early neoplastic alterations in mice.

American journal of physiology. Gastrointestinal and liver physiology·2026
Same author

Multifaceted roles of PDS5B in RAD51-dependent homology-directed DNA repair and replication fork protection.

Nature communications·2026
Same author

Zearalenone causes female reproductive lipotoxicity through the ERα-CD36/TLR4 signaling pathway.

Communications biology·2026
Same author

Comprehensive CRISPR/Cas9-based mutagenesis identifies single-amino acid substitutions that abrogate SPEN function in X inactivation.

Nature communications·2026
Same author

Corrigendum to "A novel fuzzy system-based genetic algorithm for trajectory segment generation in urban global positioning system" [J. Adv. Res. 81 (2026) 469-480].

Journal of advanced research·2026
Same author

SonoPIN enables precise, noninvasive, and efficient intracellular delivery of PROTACs.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Learning from stem cell-based embryo models.

Nature cell biology·2026
Same journal

Why the temporal dimension matters in cellular signalling.

Nature cell biology·2026
Same journal

Transcription factor condensates as storage.

Nature cell biology·2026
Same journal

Author Correction: Spatial regulation of VEGF receptor endocytosis in angiogenesis.

Nature cell biology·2026
Same journal

Mitochondria-endoplasmic reticulum contact sites as hubs where mitochondria acquire iron.

Nature cell biology·2026
Same journal

Cis and trans regulatory mechanisms of extrachromosomal DNA segregation.

Nature cell biology·2026
See all related articles

Related Experiment Video

Updated: May 1, 2026

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

707

ATM counteracts chromatin-bound cGAS during DNA replication.

Yunhao Song1, Xiaojuan Ran1, Yu Xu1,2

  • 1Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.

Nature Cell Biology
|April 29, 2026
PubMed
Summary
This summary is machine-generated.

ATM kinase counters nuclear cyclic GMP-AMP synthase (cGAS) to prevent DNA replication fork stalling. Loss of ATM triggers replication stress and interferon responses, with cGAS acting as a biomarker for ATR inhibitor therapy.

More Related Videos

Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase
07:37

Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase

Published on: September 27, 2024

2.2K
Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
10:11

Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level

Published on: July 26, 2024

1.6K

Related Experiment Videos

Last Updated: May 1, 2026

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

707
Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase
07:37

Single-Molecule Real-Time Visualization of DNA Unwinding by CMG Helicase

Published on: September 27, 2024

2.2K
Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
10:11

Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level

Published on: July 26, 2024

1.6K

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Cyclic GMP-AMP synthase (cGAS) is a DNA sensor that initiates type-I interferon responses.
  • cGAS is normally sequestered in the nucleus via chromatin binding, but its role in DNA metabolism is unclear.

Purpose of the Study:

  • To investigate the impact of chromatin-bound cGAS on DNA replication and cellular responses.
  • To elucidate the regulatory mechanisms controlling cGAS chromatin association and its functional consequences.

Main Methods:

  • Utilized cell-based assays to assess DNA replication fork dynamics and DNA fragmentation.
  • Employed genetic manipulation (ATM/ATR inhibition, cGAS depletion) to dissect regulatory pathways.
  • Investigated protein-protein interactions and phosphorylation events.

Main Results:

  • Chromatin-bound cGAS impedes DNA replication forks, causing fork slowing and nascent DNA fragmentation.
  • ATM kinase, supported by ATR, phosphorylates MRE11 to release cGAS from chromatin, thereby tolerating its nuclear presence.
  • ATM deficiency leads to replication stress, cytosolic cGAS activation, and synthetic lethality upon ATR inhibition, particularly in cancer cells.

Conclusions:

  • ATM and chromatin-bound cGAS form a regulatory circuit essential for maintaining replication homeostasis and controlling cGAS signaling in proliferating cells.
  • cGAS emerges as a potential biomarker for predicting sensitivity to ATR inhibitor therapy in ATM-deficient cancers.
  • Understanding this interplay is crucial for developing targeted cancer therapies and managing immune responses.