Mechanism of replication of DNA captured at the level of the atom

July 15, 2019) Life depends on the unwinding and separation of double stranded DNA into a single strand that can be copied for cell division. Scientists at the St. Jude Children's Research Hospital have determined by atomic resolution the structure of the machines that drive the process. The search appears today in the newspaper Nature Communications.

The process can also help solve what the principal investigator of the study has described as one of the greatest mysteries of biology: how double-stranded DNA splits into single strands to start the replication process. "Based on the crystalline structure of this research, we propose that a rotational mechanism drives transformation to initiate DNA replication," said Eric Enemark, Ph.D., associate member of the department. of structural biology of St. Jude.

Before the cells divide, their DNA needs to be accurately copied in a process called replication. This research focused on a ring-shaped enzyme called the minichromosome maintenance complex (MCM), which plays a central role. During DNA replication, the MCM complex is positioned at the fork where the double-stranded DNA splits into single strands. These strands are copied to produce a new molecule of DNA.

Enemark and his colleagues produced the first atomic resolution image of the MCM complex bound to single-stranded DNA and molecules that fuel replication.

The image captured key structural details, including the orientation of the MCM complex and single-stranded DNA. The illustrated elements show how the process works as a system of pulleys to "pull" a single strand of DNA through the MCM complex and unroll the DNA.

The same mechanism could also explain the beginning of DNA replication, Enemark said. Prior to cell division, the double-stranded DNA is encircled by two distinct enzymes of the MCM complex. Based on the newly determined structure of the replication machinery, the researchers proposed that MCM complexes begin to move in different directions, leading to the separation of double-stranded DNA into single strands.

"This unique event is at the heart of cell division and presents the essence of life in its simplest form," he said.