Target type: biologicalprocess
The controlled breakdown of nucleosomes, the beadlike structural units of eukaryotic chromatin composed of histones and DNA. [GOC:mah]
Nucleosome disassembly is a crucial process in eukaryotic cells, involving the separation of DNA from histone proteins within the nucleosome structure. This process is essential for various cellular functions, including DNA replication, transcription, and DNA repair.
**Steps involved in nucleosome disassembly:**
1. **ATP-dependent chromatin remodeling complexes:** These complexes utilize the energy from ATP hydrolysis to reposition or remove nucleosomes from DNA. Examples include SWI/SNF and CHD complexes.
2. **Histone chaperones:** These proteins bind to histone proteins, preventing their reassociation with DNA and facilitating their removal from the nucleosome. Examples include CAF-1, NAP-1, and HIRA.
3. **Histone modifications:** Specific modifications, such as acetylation, phosphorylation, and methylation, can alter histone interactions with DNA, leading to nucleosome disassembly. These modifications are catalyzed by enzymes like histone acetyltransferases (HATs), histone kinases, and histone methyltransferases (HMTs).
4. **DNA unwinding:** The unwinding of DNA by helicases can disrupt the interactions between DNA and histones, contributing to nucleosome disassembly.
5. **Other factors:** Nucleosome disassembly can also be influenced by other factors, including DNA supercoiling, DNA binding proteins, and environmental stressors.
**Mechanism of nucleosome disassembly:**
- **ATP-dependent remodeling complexes:** These complexes can slide nucleosomes along DNA, exposing specific DNA sequences for access by other factors. They can also remove histones from DNA completely, leading to nucleosome disassembly.
- **Histone chaperones:** By binding to histone proteins, chaperones prevent their reassociation with DNA and facilitate their removal from the nucleosome. They can also deliver histones to other regions of the genome for new nucleosome assembly.
- **Histone modifications:** Modifications such as acetylation can reduce the affinity of histones for DNA, promoting nucleosome disassembly. Phosphorylation and methylation can also alter histone-DNA interactions, contributing to the process.
**Importance of nucleosome disassembly:**
- **DNA replication:** Nucleosome disassembly is essential for DNA replication, allowing replication machinery access to DNA.
- **Transcription:** Nucleosome disassembly is required for transcription factors to bind to DNA and initiate transcription.
- **DNA repair:** Nucleosome disassembly allows DNA repair machinery access to damaged DNA.
Nucleosome disassembly is a highly regulated process that is essential for maintaining the integrity and proper function of eukaryotic genomes.'
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Protein | Definition | Taxonomy |
---|---|---|
ATPase family AAA domain-containing protein 2 | An ATPase family AAA domain-containing protein 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q6PL18] | Homo sapiens (human) |
ATPase family AAA domain-containing protein 2B | An ATPase family AAA domain-containing protein 2B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9ULI0] | Homo sapiens (human) |
Transcription activator BRG1 | A transcription activator BRG1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P51532] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
ferrocin c | N-methyl-2-quinolone: structure in first source | ||
gsk525762a | molibresib: mimicks acetylated histones; structure in first source | benzodiazepine | |
gsk1210151a | GSK1210151A: inhibitor of the BET family of proteins; structure in first source | imidazoquinoline | |
i-bet726 | |||
pf-06687252 | PF-06687252: a SMARCA2/4 bromodomain inhibitor; structure in first source PFI-3 : An azabicycloalkane that is (1R,4R)-2,5-diazabicyclo[2.2.1]heptane which is substituted at position 2 by a 3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl group and at position 5 by a pyridin-2-yl group. It is a potent and selective inhibitor of polybromo 1 (Kd = 48 nM), SMARCA2 and SMARCA4 (Kd = 89 nM) bromodomains. | azabicycloalkane; enone; phenols; pyridines |