On the trail of the beginning: How to find the origins of DNA replication…

DNA replication is the fundamental process that ensures that every cell within an organism contains the same hereditary information. How the DNA gets duplicated and passed on from mother to the daughter cell during cell division is already textbook knowledge. Nevertheless, it is still unclear how a cell decides where to start DNA replication. The well-known journal BioSpektrum features now an article of Elisabeth Kruse and Dr. Stephan Hamperl about how to study the start sites of replication.

The process of DNA replication; @IES

Each of our body cells safely stores and contains the same DNA content, our hereditary information. In order to pass it from mother to the daughter cell, the DNA has to be duplicated beforehand. The process responsible for making an accurate copy of the DNA is called replication.

In order to duplicate the DNA, the two sister DNA strands that form a double helix have to be separated. The DNA double helix looks like a zipper, which gets unzipped when replication starts. Each of the two single DNA strands serve as templates for building a new second strand and following replication, both new DNA double strands consist of an old and a newly synthesized DNA sister strand. 

In contrast to a zipper, which can only be opened and closed at one end, the DNA replication machinery can start from everywhere. Well, not really from everywhere, it starts at specific DNA regions that are called origins of replication (ORIs). More than 60,000 ORIs exist in our DNA. However, only a 20% to 30% are activated, which still is enough to duplicate the DNA within just 6 - 8 h of S-phase. The residual ORIs can be activated randomly or serve as back up. Interestingly, cells, even if they belong to same cell type, activate different ORIs and additionally, ORIs are not activated at the same time. So, how can a cell decide which ORIs should be activated and which not and how does it coordinate the ORI activation?

Over the recent years, many experimental methodologies have been developed to unravel the processes underlying ORI activation. Still, there is no method that allows a comprehensive analysis of ORIs. In the article published in BioSpektrum, Elisabeth Kruse and Dr. Hamperl from the Institute for Epigenetics and Stem Cells recapitulate current state-of-the-art methods and introduce an alternate method for analyzing ORIs, which could have the potential to elucidate which ORIs gets activated and how often, and which factors play a major role in ORI regulation.

The article is only available in German. Check it out here.