regulation of DNA biosynthetic process

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of DNA biosynthetic process. [GOC:obol]

The regulation of DNA biosynthetic process is a complex and tightly controlled process that ensures accurate and efficient replication of the genome. It involves a coordinated interplay of numerous proteins, enzymes, and regulatory elements. Here is a detailed description:

**1. Initiation:**
* **Origin Recognition Complex (ORC):** ORC binds to specific DNA sequences called origins of replication, marking the starting points for DNA replication.
* **Cdc6 and Cdt1:** These proteins help load the MCM helicase onto the DNA, forming the prereplicative complex (pre-RC).
* **Licensing factor:** The pre-RC formation is termed "licensing" and ensures that each origin is only replicated once per cell cycle.
* **Cyclin-dependent kinases (CDKs):** At the onset of S phase, CDKs are activated and phosphorylate various proteins, including Cdc6 and Cdt1, leading to their inactivation and preventing the assembly of additional pre-RCs.

**2. Unwinding and Replication Fork Formation:**
* **MCM helicase:** Once activated, MCM helicase unwinds the DNA double helix, separating the two strands.
* **Single-stranded DNA binding proteins (SSBs):** These proteins stabilize the separated strands, preventing them from re-annealing.

**3. Primer Synthesis:**
* **Primase:** An RNA polymerase that synthesizes short RNA primers complementary to the DNA template, providing a starting point for DNA polymerase.

**4. DNA Polymerase Activity:**
* **DNA polymerase α:** Initiates DNA synthesis by extending the RNA primers.
* **DNA polymerase δ and ε:** These high-fidelity polymerases take over DNA synthesis, extending the primers and creating long DNA strands.
* **Proofreading activity:** DNA polymerases possess proofreading activity, ensuring accuracy in DNA replication.

**5. Okazaki Fragment Synthesis:**
* **Leading strand:** Synthesis occurs continuously in the 5' to 3' direction, following the unwinding of the DNA.
* **Lagging strand:** Synthesis occurs discontinuously in short fragments called Okazaki fragments.
* **DNA ligase:** Joins the Okazaki fragments, forming a continuous strand.

**6. Termination:**
* **Replication termination sequences:** These sequences signal the end of DNA replication.
* **Specific proteins:** Bind to these sequences and facilitate the separation of the replicated DNA molecules.

**7. Regulation:**
* **Cell cycle checkpoints:** Monitor the progress of DNA replication and ensure that it is completed accurately before entering the next stage of the cell cycle.
* **Transcription factors:** Regulate the expression of genes involved in DNA replication.
* **Signaling pathways:** Various signaling pathways, such as the p53 pathway, can influence DNA replication by affecting the activity of key regulatory proteins.

**8. Post-replication Repair:**
* **DNA damage:** Errors or damage introduced during replication can be repaired by various mechanisms, including mismatch repair and nucleotide excision repair.

**9. Telomere Replication:**
* **Telomeres:** Protective caps at the ends of chromosomes, shorten with each round of replication.
* **Telomerase:** An enzyme that adds repetitive DNA sequences to the ends of chromosomes, preventing their degradation.

The regulation of DNA biosynthetic process is essential for maintaining the integrity of the genome and ensuring proper cell division. Dysregulation of this process can lead to genomic instability and contribute to various diseases, including cancer.'
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