Related Experiment Video

Updated: Mar 31, 2026

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins
12:47

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins

Published on: December 27, 2016

19.6K

ATM-Dependent Phosphorylation of All Three Members of the MRN Complex: From Sensor to Adaptor

Martin F Lavin1, Sergei Kozlov2, Magtouf Gatei3

  • 1UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD 4029, Australia. m.lavin@uq.edu.au.

Biomolecules
|October 30, 2015
PubMed

Insights

The Mre11/Rad50/Nbs1 (MRN) complex acts as an adaptor, mediating ATM signaling for DNA double-strand break (DSB) repair. This interaction is crucial for cell cycle control, DNA repair, and cell fate.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA double-strand breaks (DSB) pose a significant threat to genome integrity.
  • Mutations in DSB repair proteins are linked to genetic disorders, cancer, and neurodegeneration.
  • ATM and the MRN complex are critical for recognizing and signaling DSBs.

Purpose of the Study:

  • To elucidate the interplay between ATM and the MRN complex in DSB signaling.
  • To highlight the MRN complex's adaptor role in mediating ATM signaling.
  • To understand how this interaction controls downstream cellular processes.

Main Methods:

  • Focus on the molecular mechanisms of DNA damage response.
  • Investigate protein-protein interactions between ATM and MRN complex components.
  • Analyze the consequences of ATM-MRN interactions on downstream signaling pathways.

Main Results:

  • The MRN complex rapidly localizes to DSBs and facilitates ATM activation.
  • ATM phosphorylates MRN complex members, initiating downstream signaling cascades.
  • The MRN complex serves as a pivotal adaptor, channeling ATM signaling to regulate cell cycle, repair, and survival.

Conclusions:

  • The MRN complex is essential for initiating and mediating ATM-dependent signaling following DSBs.
  • This interaction is fundamental for maintaining genome stability and cellular homeostasis.
  • Dysregulation of this pathway has implications for various pathologies.
Keywords:
ATM activationDNA double strand breaksMre11/Rad50/Nbs1 complexadaptor roleoxidative stressphosphorylation

More Related Videos

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

7.1K
Oligopeptide Competition Assay for Phosphorylation Site Determination09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

9.0K

Related Concept Videos

ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
18.8K
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
3.0K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
7.0K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.7K
ATP Synthase: Structure01:18

ATP Synthase: Structure

ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
17.5K
The ADP/ATP Carrier Protein01:42

The ADP/ATP Carrier Protein

ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
4.6K