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Updated: Mar 7, 2026

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
The Intra-S Checkpoint Responses to DNA Damage
Divya Ramalingam Iyer1, Nicholas Rhind2
1Department of Biochemistry & Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. DivyaRamalingam.Iyer@umassmed.edu.
The intra-S checkpoint protects genome integrity during DNA replication by regulating replication forks. This review clarifies its critical roles in preventing genomic instability following DNA damage.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA replication is vulnerable to damage from genotoxins, threatening genomic integrity.
- The intra-S checkpoint is activated during S phase to safeguard DNA duplication.
- This checkpoint regulates origin firing, fork progression, and gene transcription.
Purpose of the Study:
- To review the critical functions of the intra-S checkpoint at replication forks.
- To elucidate the checkpoint's role in preventing genomic instability after DNA damage.
- To identify factors targeted by the checkpoint at stalled replication forks.
Main Methods:
- Review of existing literature on DNA replication and the intra-S checkpoint.
- Analysis of studies investigating replication fork dynamics and stability.
- Discussion of molecular pathways activated by the checkpoint in response to DNA damage.
Main Results:
- The intra-S checkpoint plays a crucial role in regulating replication fork progression and stability.
- The exact mechanisms and targets of the checkpoint at stalled forks are still debated.
- The checkpoint is essential for preventing genomic instability by managing fork dynamics.
Conclusions:
- The intra-S checkpoint is vital for maintaining genomic stability during DNA replication.
- Further research is needed to fully understand the checkpoint's precise mechanisms at replication forks.
- Understanding these pathways is key to preventing replication-associated genomic instability.
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