DNA replication-dependent chromatin assembly

Definition

Target type: biologicalprocess

The formation of nucleosomes on newly synthesized DNA, coupled to strand elongation. [GOC:mah, PMID:28053344]

DNA replication-dependent chromatin assembly is a tightly regulated process that ensures the faithful duplication of the genome and the proper inheritance of epigenetic information during cell division. It involves the coordinated action of various factors that work together to assemble new nucleosomes on newly synthesized DNA. The process can be divided into several key steps:

1. **Pre-RC formation:** Prior to the initiation of DNA replication, an origin recognition complex (ORC) binds to specific DNA sequences called origins of replication. This is followed by the recruitment of Cdc6 and Cdt1, which facilitate the loading of the MCM2-7 helicase complex. This complex forms the pre-replication complex (pre-RC) and marks origins for potential replication initiation.

2. **Replication initiation:** During S phase, cyclin-dependent kinases (CDKs) are activated and phosphorylate key components of the pre-RC. This phosphorylation triggers the recruitment of additional factors, including DNA polymerase alpha/primase complex and CMG helicase, which initiates DNA unwinding and replication fork formation.

3. **Nucleosome assembly on nascent DNA:** As the replication fork progresses, the newly synthesized DNA strands become available for nucleosome assembly. This process is tightly coupled with DNA replication and involves several key players:
* **Histone chaperones:** These proteins bind to histones and facilitate their delivery to the replication fork. Some of the key histone chaperones involved in replication-dependent chromatin assembly include CAF-1, NAP-1, and HIRA.
* **Histone modifying enzymes:** Histone acetylation, methylation, and phosphorylation play crucial roles in regulating nucleosome assembly and chromatin structure. These modifications can influence histone binding affinity, DNA accessibility, and the recruitment of other chromatin-associated proteins.
* **DNA-dependent protein kinase (DNA-PK):** This kinase is involved in the phosphorylation of histone H2AX, a key event in the assembly of the DNA damage response complex.
* **ATRX:** This protein is responsible for the deposition of the histone variant H3.3 at specific genomic regions.

4. **Chromatin remodeling complexes:** These complexes, such as SWI/SNF, are essential for altering chromatin structure and facilitating DNA accessibility for replication, transcription, and other DNA-dependent processes. They can reposition, evict, or remodel nucleosomes, thus playing a vital role in maintaining chromatin dynamics during replication.

5. **Epigenetic inheritance:** During DNA replication, the parental epigenetic information is copied onto the newly synthesized DNA. This process involves the recognition of pre-existing histone modifications by specific reader proteins, which then recruit histone modifying enzymes to establish similar modifications on the newly assembled nucleosomes.

6. **Replication checkpoint control:** The replication process is tightly regulated by checkpoints that ensure the accuracy and completeness of DNA duplication. If errors occur, the checkpoints can activate a signal transduction cascade that arrests cell cycle progression until the errors are corrected.

In summary, DNA replication-dependent chromatin assembly is a complex and highly regulated process that ensures the proper inheritance of genetic and epigenetic information during cell division. It involves the coordinated action of numerous factors, including histone chaperones, histone modifying enzymes, chromatin remodeling complexes, and checkpoint control mechanisms. The fidelity of this process is crucial for maintaining genome integrity and ensuring the proper function of the cell.'
"

Proteins (1)

Compounds (3)