Related Experiment Video
Updated: Aug 30, 2025
07:37
Author Spotlight: Unraveling the Dynamics of Eukaryotic DNA Replication Through Single-Molecule Visualization
Published on: September 27, 2024
1.7K
A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress
Wezley C Griffin1,2, David R McKinzey1, Kathleen N Klinzing1
1Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
Nature Communications
|August 30, 2022
Summary
Minichromosome maintenance (MCM) 8/9 helicase promotes DNA replication fork progression and genome stability. Loss of MCM8 or 9 impairs replication and increases DNA damage, highlighting its crucial role in cellular repair.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The minichromosome maintenance (MCM) 8/9 helicase is a AAA+ complex with homology to MCM2-7.
- Its precise cellular function in DNA replication and repair remains largely undefined.
Purpose of the Study:
- To investigate the role of MCM8/9 in DNA synthesis and replication fork stability.
- To elucidate the specific functions of MCM8/9 in normal replication and in response to replication stress.
Main Methods:
- Analysis of DNA synthesis and replication fork stability in cells lacking MCM8 or MCM9.
- Assessment of nascent strand degradation and genomic damage markers.
Main Results:
- MCM8/9 activity is functionally partitioned between promoting replication fork progression and protecting stalled forks.
- Loss of MCM8 or 9 slows replication rate and leads to excessive nascent strand degradation.
- MCM8/9 directs downstream stabilizers like BRCA1 and Rad51 to protect stalled forks.
Conclusions:
- MCM8/9 plays a multifunctional role in DNA replication, aiding normal fork progression.
- MCM8/9 is critical for protecting stalled replication forks from degradation, thereby maintaining genome integrity under stress.
Related Concept Videos
02:37Restarting Stalled Replication Forks
5.9K
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,...
5.9K
01:02The DNA Replication Fork
36.5K
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
36.5K
02:31Homologous Recombination
50.9K
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...
50.9K
00:55DNA Helicases
22.0K
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...
22.0K
02:37DNA Damage can Stall the Cell Cycle
9.3K
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...
9.3K
01:29Replication in Eukaryotes
14.2K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
14.2K