Unknown mechanism of cell division revealed

Molecular biologists have identified a complex of proteins in cells that help control the pause or complete stop of DNA replication, ensuring the process runs smoothly.

The process of DNA replication involves many protein complexes with highly specialized functions, including participation in the unwinding of the DNA double helix and the copying of both strands of DNA. Previous studies have shown that there are proteins that stop replication along the leading strand of DNA. However, it remained a mystery how replication stops on the lagging strand.

Both strands in the DNA double helix are directed in opposite directions. When the helix unwinds to form a fork, a seed is attached to the leading strand, which becomes the front part of the new strand, continuously growing nucleotide by nucleotide. However, in this case, the second strand, called the lagging strand, waits for the DNA to unwind enough so that it can attach a primer, called an Okazaki fragment, to begin synthesizing the strand in the direction opposite to the point of unwinding.

To determine the mechanism of lagging strand replication arrest, the researchers used cryoelectron microscopy, CRISPR-based mutation analysis, and other advanced methods to identify the protein complex. It turned out that four proteins combined into the 55LCC complex play a key role in this process. They bind to DNA and the replication complex, allowing the latter to be digested by enzymes.

At the same time, 55LCC is important for ensuring the entire process of DNA replication, so the absence of this complex leads to the cessation of normal cell division. Mutations in the genes encoding proteins of this complex can cause various diseases, including hearing loss, cognitive and motor impairment, and epilepsy.