Related Experiment Video

Updated: Jan 10, 2026

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

3.5K

TIPIN coordinates ATM-dependent checkpoint and NF-κB signaling to counteract DNA replication damage from

Arafat Khan1, Justin F Lim1, Natalie Lo1

  • 1Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York, USA.

Communications Biology
|November 25, 2025
PubMed

Insights

TIPIN amplifies ATM signaling to enhance DNA repair during replication stress. This pathway, involving MDC1 and NF-κB, increases cancer therapy effectiveness by promoting cell death.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • ATM kinase regulates cellular responses to DNA double-strand breaks (DSBs) caused by anti-cancer therapies.
  • Replication stress is a critical challenge during cancer treatment.

Purpose of the Study:

  • To investigate the role of TIPIN in coordinating ATM signaling during DNA replication stress.
  • To elucidate the molecular mechanisms by which TIPIN influences DNA repair and cellular responses to genotoxic therapy.

Main Methods:

  • Investigated the interaction and phosphorylation of TIPIN by ATM.
  • Assessed the recruitment of MDC1 to stalled replication forks.
  • Analyzed the impact of MDC1 depletion on NF-κB signaling and apoptosis.
  • Evaluated the effect of targeting the ATM-TIPIN-MDC1 pathway on cancer cell cytotoxicity.

Main Results:

  • TIPIN acts as a key coordinator of ATM signaling in response to replication stress.
  • TIPIN amplifies ATM signaling, promoting DNA end resection and homology-directed repair.
  • Phosphorylated TIPIN is essential for MDC1 recruitment, ATM-dependent NF-κB activation, and c-FLIP regulation.
  • MDC1 depletion potentiates caspase-8 activation and cytotoxicity of topoisomerase inhibitors.

Conclusions:

  • TIPIN is a master regulator of ATM-dependent DNA double-strand break repair and NF-κB signaling.
  • Targeting MDC1 enhances the effectiveness of genotoxic cancer therapy by suppressing senescence and increasing cytotoxicity.

More Related Videos

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

14.6K
Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication05:55

Author Spotlight: Unveiling the Role of SNF2L in Replication Fork Stability and Genome Duplication

Published on: August 23, 2024

987

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

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...
9.9K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

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...
3.0K
DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
34.7K
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,...
6.2K
The DNA Replication Fork01:02

The DNA Replication Fork

An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork.   Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
40.3K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.2K