Related Experiment Video

Updated: Apr 23, 2026

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.1K

FBXL5-mediated degradation of single-stranded DNA-binding protein hSSB1 controls DNA damage response

Zhi-Wei Chen1, Bin Liu2, Nai-Wang Tang1

  • 1Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.

Nucleic Acids Research
|September 25, 2014
PubMed

Insights

The E3 ligase Fbxl5 targets human single-strand DNA binding protein 1 (hSSB1) for degradation, impacting DNA damage response. Inhibiting Fbxl5 may offer a therapeutic strategy for lung cancers.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • DNA Repair Mechanisms

Background:

  • Human single-strand DNA binding protein 1 (hSSB1) is crucial for DNA damage response and genome stability.
  • ATM-dependent signaling regulates hSSB1 stability through phosphorylation, preventing its degradation.
  • The specific E3 ligase responsible for hSSB1 ubiquitination remained unidentified.

Purpose of the Study:

  • To identify the E3 ligase targeting hSSB1 for degradation.
  • To elucidate the role of Fbxl5 in regulating hSSB1 stability and DNA damage response.
  • To investigate the therapeutic potential of targeting Fbxl5 in lung cancer.

Main Methods:

  • Investigated the interaction between Fbxl5 and hSSB1.
  • Assessed the ubiquitination and degradation of hSSB1 mediated by Fbxl5.
  • Examined the effect of Fbxl5 overexpression on DNA damage response pathways (ATM activation, checkpoint signaling).
  • Analyzed hSSB1 and Fbxl5 protein levels in lung cancer cell lines and patient samples.

Main Results:

  • Identified Fbxl5 as the bona fide substrate recognition component of an SCF E3 ligase targeting hSSB1.
  • Demonstrated that ATM-mediated phosphorylation of hSSB1 at T117 prevents Fbxl5-induced degradation.
  • Showed that Fbxl5 overexpression impairs DNA double-strand break (DSB) response, leading to increased sensitivity to genotoxic agents and defective checkpoint activation.
  • Observed an inverse correlation between hSSB1 and Fbxl5 protein levels in lung cancer.

Conclusions:

  • Fbxl5 negatively regulates hSSB1, impacting DNA damage response pathways.
  • Fbxl5 plays a critical role in cellular sensitivity to DNA damaging agents.
  • Fbxl5 represents a potential therapeutic target for enhancing lung cancer treatment.

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

13.8K
Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage10:44

Laser Microirradiation to Study In Vivo Cellular Responses to Simple and Complex DNA Damage

Published on: January 31, 2018

9.8K

Related Concept Videos

Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
12.7K
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.0K
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

3.4K
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...
8.5K
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...
2.3K
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,...
5.0K