Related Experiment Video

Updated: Jan 28, 2026

Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice
17:59

Derivation of Thymic Lymphoma T-cell Lines from Atm-/- and p53-/- Mice

Published on: April 3, 2011

12.7K

MRE11 UFMylation promotes ATM activation

Zhifeng Wang1,2, Yamin Gong1,3, Bin Peng1

  • 1Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China.

Nucleic Acids Research
|February 21, 2019
PubMed

Insights

Ubiquitin-fold modifier 1 (UFMylation) of MRE11 is crucial for DNA double-strand break (DSB) repair and genome stability. This UFMylation is essential for optimal ATM kinase activation and DNA repair complex formation.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • A robust DNA damage response (DDR) is vital for maintaining genome integrity and preventing cancer.
  • DNA double-strand breaks (DSBs) are highly toxic lesions repaired via ATM kinase-mediated pathways.
  • The role of ubiquitin-fold modifier 1 (UFMylation) in DDR is largely unexplored.

Purpose of the Study:

  • To investigate the function of UFMylation in the DNA damage response.
  • To determine if MRE11 protein is subject to UFMylation and its impact on DNA repair.

Main Methods:

  • Investigated MRE11 UFMylation at K282 using biochemical assays.
  • Assessed the impact of MRE11 UFMylation on MRN complex formation.
  • Evaluated the role of MRE11 UFMylation in ATM activation and DNA repair via homologous recombination.
  • Analyzed a pathogenic MRE11 mutation (G285C) found in uterine endometrioid carcinoma.

Main Results:

  • MRE11 protein undergoes UFMylation on lysine 282 (K282).
  • MRE11 UFMylation is essential for MRN complex formation and optimal ATM activation following DSBs.
  • UFMylation of MRE11 is required for efficient homologous recombination repair and genome stability.
  • A pathogenic MRE11 mutation (G285C) phenocopies the defects observed in UFMylation-deficient MRE11 mutants.

Conclusions:

  • MRE11 UFMylation is a critical regulatory mechanism in the DNA double-strand break response.
  • This modification promotes ATM activation, DNA repair, and maintains genome stability.
  • MRE11 UFMylation represents a potential therapeutic target for diseases involving genomic instability.

More Related Videos

Plant Promoter Analysis: Identification and Characterization of Root Nodule Specific Promoter in the Common Bean10:58

Plant Promoter Analysis: Identification and Characterization of Root Nodule Specific Promoter in the Common Bean

Published on: December 23, 2017

13.0K
Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions10:16

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

Published on: June 28, 2018

33.4K

Related Concept Videos

The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.8K
The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

3.9K
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...
3.4K
Models of Health Promotion and Illness Prevention II01:18

Models of Health Promotion and Illness Prevention II

The person's health status fluctuates continually, varying from being in good health to becoming ill and returning to being healthy. To understand the concept of illness prevention, there are two models. First, the health-illness continuum model is a graphic representation of an individual's wellness. It states that a person is considered healthy in the absence of physical disease and the presence of good emotional health.
The agent-host-environment model states that disease results...
2.1K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.6K
Prokaryotic Transcriptional Activators and Repressors01:58

Prokaryotic Transcriptional Activators and Repressors

The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
25.4K