Increasing our understanding of DNA replication
A team of scientists from the University of Hong Kong, the Hong Kong University of Science and Technology, and Institut Curie in France have made significant strides in understanding the mystery of DNA replication. They studied the role of the minichromosome maintenance protein complex (MCM) which is vital to the process of DNA replication during cell division.
The researchers utilized cryogenic electron microscopy to visualize an MCM structure as it unwound a segment of human DNA. Unexpectedly, they found that even ‘dormant’ MCMs have already initiated the DNA unwinding process. This contradicts earlier studies in yeast which proposed that MCMs needed to be activated before beginning to untwist DNA.
Dr Alessandro Costa of the Francis Crick Institute in London, praised the research, saying, “It is a technical tour-de-force and a very thorough study... It does contain really surprising information because it highlights differences between the human system and yeast systems that explain a number of findings that we couldn’t rationalise earlier.”
In addition to this, the research discovered that unlike in yeast, where replication initiation is pinpointed by a specific genetic sequence, human DNA replication seems to be influenced by a more complex genetic ‘landscape’. Importantly, the team also noticed that the human DNA double helix is already slightly untwisted even when the MCM complex is inactive.
Professor Tye Bik-Kwoon, a co-author of the paper, explained the novelty of their findings, stating, “For yeast, we know the site of replication initiation is fixed; we know the sequence. But in human cells, our paper shows that the loading mechanism is actually quite different.”
This research has the potential to clarify the origins of some genetic disorders and cancers, as well as pave the way for advancements in biotechnology and next-generation medicinal therapies. Yet, as Dr Zhai Yuanliang, the team leader from the University of Hong Kong, cautioned, this is only one of many possible interpretations, and additional research is needed to solidify these findings and fully comprehend the intricacies of DNA replication