New Research Reveals the Intricate Process of DNA Replication
Every person starts as a single fertilized egg, which eventually develops into trillions of cells by adulthood. These cells continuously divide to create fresh human cells, but the process of DNA replication is not as simple as it may seem.
A new study published in the Annual Review of Biochemistry sheds light on the challenges faced by cells during DNA replication. The average dividing cell needs to copy 3.2 billion base pairs of DNA perfectly every 24 hours. While the cell’s replication machinery works at an impressive pace of 50 base pairs per second, it is still too slow to duplicate the entire human genome.
To overcome this obstacle, cells start replication at multiple spots. Yeast cells have hundreds of potential replication origins, while animals like mice and humans have tens of thousands. However, this poses a new challenge of knowing where to start and how to time everything accurately to avoid mistakes.
Without precise control, some DNA may get copied twice, leading to cellular pandemonium. This process becomes even more critical as problems during DNA replication can cause disorganization of the genome, which is often a precursor to cancer. Genetic diseases can also result from issues with DNA replication.
Researchers are now making progress in understanding the molecular checks and balances that ensure each origin initiates DNA copying once and only once, producing a precise, complete new genome. The goal is to replicate DNA correctly and efficiently.
The process of DNA replication is a two-step process that involves controlling the actions of a crucial enzyme called a helicase. The first step involves loading inactive helicases onto the DNA at the replication origins, while the second step activates the helicases to unwind the DNA for copying.
Scientists have identified a cluster of six proteins called ORC that sit at the origins and slide onto the DNA strands. In baker’s yeast, these start sites are easily identifiable, but in humans and other complex organisms, the start sites are not as clear. Replication seems to initiate where the tightly spooled genome has loosened. The initiation of DNA replication occurs during a specific phase of the cell cycle known as G1.
Protein levels, particularly a protein called CDK, play a critical role in controlling DNA replication. Low levels of CDK allow helicases to bind and initiate replication, while high levels prevent repeat binding, ensuring replication only occurs once.
Once ORC settles onto the DNA, it attracts a complex of proteins, including helicases, which eventually unwind the DNA. Activation of the helicases is triggered by a molecule called CDK, which signals other proteins to join the process. The helicases then push and pull on the DNA strands, separating the weak hydrogen bonds holding them together.
The two helicases undergo a positional change, allowing them to untwist the DNA between them and proceed with replication. Each helicase moves in the opposite direction, leaving the origin behind and copying the DNA letters as they are freed.
The entire process of DNA replication in human cells takes approximately eight hours. However, there is still much to learn, especially regarding how other proteins and structures, such as histones and gene-regulating proteins, interact and avoid interfering with the replication process.
Understanding the intricacies of DNA replication is essential for unraveling various genetic diseases and preventing the development of conditions such as cancer. The recent research provides valuable insights into this remarkable biological process, laying the groundwork for further discoveries in the field.