Related Experiment Video

Updated: Jul 28, 2025

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
06:25

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence

Published on: February 10, 2023

2.1K

APOBEC3B coordinates R-loop to promote replication stress and sensitize cancer cells to ATR/Chk1 inhibitors

Chunyan Zong1,2,3, Zhe Zhang1,2,3, Li Gao4

  • 1Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Cell Death & Disease
|June 3, 2023
PubMed

Insights

Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) promotes cancer genomic instability by creating R-loops. Targeting this mechanism may enhance cancer therapy effectiveness.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B, A3B) is a known driver of cancer mutations.
  • Its precise role in replication stress (RS) and potential therapeutic exploitation remain unclear.

Purpose of the Study:

  • To elucidate the function of A3B in replication stress.
  • To investigate whether A3B's mechanism can be targeted for cancer therapy.

Main Methods:

  • Immunoprecipitation-mass spectrometry (IP-MS) was used to identify A3B binding partners.
  • R-loop formation and distribution were analyzed upon A3B overexpression.
  • The effect of Ribonuclease H1 (RNASEH1) on A3B-induced RS was assessed.
  • Sensitivity to ATR/Chk1 inhibitors (ATRi/Chk1i) was evaluated in melanoma cells.

Main Results:

  • A3B was identified as a novel binding component of R-loops.
  • A3B overexpression exacerbated RS by promoting R-loop formation and altering their genomic distribution.
  • Ribonuclease H1 (RNASEH1) rescued A3B-induced replication stress.
  • High A3B levels correlated with sensitivity to ATRi/Chk1i in melanoma, dependent on R-loop status.

Conclusions:

  • A3B promotes replication stress in cancer through R-loop formation.
  • The findings reveal a mechanistic link between A3B, R-loops, and replication stress.
  • This study provides a basis for developing biomarkers to predict patient response to ATRi/Chk1i therapy.

More Related Videos

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

571
Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.3K

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:37

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...
9.2K
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,...
5.8K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K
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.
35.5K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K