Related Experiment Video
Updated: Jul 6, 2026
08:44
Generation and Purification of Human INO80 Chromatin Remodeling Complexes and Subcomplexes
Published on: October 23, 2014
The Ino80 chromatin-remodeling enzyme regulates replisome function and stability
Manolis Papamichos-Chronakis1, Craig L Peterson
1Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Biotechnology 2, Suite 210, Worcester, Massachusetts 01605, USA.
Nature Structural & Molecular Biology
|April 1, 2008
Summary
The Ino80 enzyme is crucial for DNA replication fork progression and stability, particularly under replication stress. It ensures proper replisome function and restart following fork stalling.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- ATP-dependent chromatin remodelers are vital for transcription and DNA repair.
- The role of chromatin remodeling in DNA replication remains underexplored.
Purpose of the Study:
- To investigate the function of the Ino80 chromatin remodeler during DNA replication.
- To determine Ino80's role in replication fork progression and stability.
Main Methods:
- Utilized inducible degradation of Ino80 in cells.
- Analyzed replication fork dynamics and replisome stability under replication stress.
- Studied the impact of Ino80 depletion on DNA replication fidelity.
Main Results:
- Ino80 is recruited to replication origins during S phase.
- Ino80 is essential for efficient replication fork progression, especially under low replication stress.
- Stalling replication forks in Ino80-deficient cells leads to replisome dissociation and is lethal.
- Ino80 stabilizes stalled replication forks, facilitating proper restart.
Conclusions:
- Ino80's chromatin-remodeling activity is critical for regulating replication fork progression.
- Ino80 plays a key role in maintaining replisome stability and ensuring DNA replication restart after stalling.
Related Concept Videos
02:54Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
03:01The Replisome
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
03:01The Replisome
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with the...
02:37Restarting 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, a...
02:41Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...