nuclear replication fork

Definition

Target type: cellularcomponent

The Y-shaped region of a nuclear replicating DNA molecule, resulting from the separation of the DNA strands and in which the synthesis of new strands takes place. Also includes associated protein complexes. [GOC:jl, GOC:mtg_sensu]

The nuclear replication fork is a complex molecular machine responsible for replicating DNA during the S phase of the cell cycle. It is composed of a multitude of proteins that work together to unwind the DNA double helix, separate the strands, and synthesize new complementary strands. The cellular components of the replication fork can be broadly categorized into three main groups:

1. **DNA unwinding and stabilization:**
- **Helicases:** These enzymes unwind the DNA double helix, breaking the hydrogen bonds between the two strands. In eukaryotes, the primary helicase involved is CMG (composed of Cdc45, Mcm2-7, and GINS).
- **Single-strand binding proteins (SSBs):** Once the strands are separated, SSBs bind to the single-stranded DNA, preventing them from re-annealing and protecting them from degradation. Replication protein A (RPA) is the major SSB in eukaryotes.
- **Topoisomerases:** These enzymes relieve the torsional stress that builds up ahead of the replication fork as the DNA unwinds. Type I topoisomerases cleave one strand of DNA to allow rotation, while type II topoisomerases cleave both strands to pass another DNA segment through the break.

2. **DNA synthesis:**
- **DNA polymerase alpha/primase:** This complex initiates DNA synthesis by laying down a short RNA primer, which is then extended by DNA polymerase alpha.
- **DNA polymerase epsilon and delta:** These are the main replicative DNA polymerases in eukaryotes. They extend the primer and synthesize the new DNA strand in a 5' to 3' direction.
- **PCNA (Proliferating Cell Nuclear Antigen):** This ring-shaped protein acts as a sliding clamp, keeping the DNA polymerase associated with the template strand during DNA synthesis.

3. **DNA repair and checkpoint control:**
- **DNA repair proteins:** These proteins ensure the fidelity of DNA replication by detecting and correcting errors that may arise during the process.
- **Checkpoint proteins:** These proteins monitor the progress of DNA replication and activate cell cycle checkpoints if errors occur, pausing the cell cycle until the errors are repaired.

The replication fork is highly dynamic and constantly moving along the DNA molecule as it replicates. Its structure and components are tightly regulated to ensure that DNA is copied accurately and efficiently. These components work together in a coordinated manner to achieve the essential task of replicating the genome, ensuring the faithful transmission of genetic information from one generation to the next.'"

Proteins (4)

Compounds (64)