Replisome

DNA replication en

Linear DNA Supercoiling

PDB 1jmc EBI

1axc tricolor

Replisome is a complex molecular machine involved in the DNA replication process. The replisome plays a crucial role in cell division, ensuring that the DNA of the parent cell is accurately copied and passed on to the daughter cells. This process is fundamental to genetic inheritance, cell growth, and the maintenance of genetic stability across generations.

Structure and Function

The replisome is composed of multiple proteins and enzymes that work together to replicate DNA. The core components include:

• DNA helicase: Unwinds the double-stranded DNA, creating two single strands that serve as templates for replication.
• DNA polymerase: Synthesizes new DNA strands by adding nucleotides complementary to the template strand.
• Primase: Synthesizes short RNA primers that are necessary for DNA polymerase to initiate DNA synthesis.
• Sliding clamp: Increases the processivity of DNA polymerase, allowing it to synthesize long stretches of DNA without dissociating from the template.
• Clamp loader: Responsible for loading the sliding clamp onto DNA.

The replisome assembles at the origin of replication, a specific sequence in the DNA where replication begins. The process of replication involves the separation of the DNA strands by DNA helicase, followed by the synthesis of leading and lagging strands. The leading strand is synthesized continuously in the direction of the replication fork movement, while the lagging strand is synthesized discontinuously in the form of Okazaki fragments. The replisome ensures that both strands are replicated simultaneously and accurately.

Regulation

The activity of the replisome is tightly regulated to ensure that DNA replication occurs only once per cell cycle. This regulation involves a complex network of signal transduction pathways and protein-protein interactions that control the assembly and disassembly of the replisome, the initiation of replication, and the response to replication stress or DNA damage.

Relevance to Disease

Errors in DNA replication can lead to mutations and genomic instability, contributing to the development of cancer and other genetic diseases. Understanding the mechanisms of replisome function and regulation can provide insights into the causes of these diseases and lead to the development of new therapeutic strategies.