Related Experiment Video

Updated: May 17, 2025

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
06:24

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51

Published on: February 13, 2019

7.9K

Dynamic conformations of the P. furiosus MR-DNA complex link Mre11 nuclease activity to DNA-stimulated Rad50 ATP

Marella D Canny1, Mahtab Beikzadeh2, Navneet Kaur2,3

  • 1Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA.

Communications Biology
|April 2, 2025
PubMed

Insights

The MRE11-RAD50-NBS1/Xrs2 (MRN/X) complex, crucial for DNA repair, exists in dynamic conformations. DNA binding reveals a link between Mre11 nuclease activity and Rad50 ATP hydrolysis, coordinating repair functions.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • The MRE11-RAD50-NBS1/Xrs2 (MRN/X) complex is vital for DNA damage repair.
  • Existing structural data suggests heterogeneity in the MR complex, implying uncharacterized conformational states.

Purpose of the Study:

  • To determine the ensemble of distinct conformations of the MR complex when bound to DNA.
  • To investigate the functional implications of these dynamic conformations in DNA repair.

Main Methods:

  • Methyl-based NMR experiments were employed on the P. furiosus MR complex.
  • In vitro activity assays were performed on MR mutants.

Main Results:

  • An ensemble of distinct conformations of the DNA-bound MR complex was determined, highlighting its dynamic nature.
  • A significant correlation was observed between Mre11 nuclease activity and DNA-stimulated ATP hydrolysis by Rad50.
  • Structural and activity data support a model where ATP hydrolysis by Rad50 facilitates access to Mre11 active sites.

Conclusions:

  • The study elucidates dynamic conformations of the DNA-bound MR complex, crucial for DNA repair.
  • This work provides a foundation for understanding how conformational heterogeneity coordinates MR complex functions in maintaining genome stability.

More Related Videos

Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.1K
Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair10:59

Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair

Published on: May 24, 2017

9.4K

Related Concept Videos

Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
49.9K
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,...
5.7K
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. ...
30.7K
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...
9.0K
DNA Helicases00:55

DNA Helicases

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
21.0K
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...
13.8K