Molecular motors race during DNA replication

A collaboration between the King Abdullah University of Science and Technology (KAUST) and Australia's University of Wollongong has unveiled the molecular mechanics controlling a key step in DNA replication, improving our understanding of fundamental biological processes.

Processes such as DNA replication, repair and transcription involve a complex choreography of molecular motors. 

This study is the first to show how the relative rates of these motors affect their interaction with double-stranded DNA binding proteins.

In the circular Escherichia coli chromosome, replicating DNA splits into two forks heading in opposite directions. Convergence of the forks is regulated by directional barriers that consist of Tus proteins bound to Ter sites to block oncoming replication forks.

The researchers, led by Samir Hamdan at KAUST, monitored DNA replication machinery in real time and found that the efficiency of the Tus–Ter block depends on how quickly the replication fork is moving. Tus has to rearrange its connection to the DNA strand when the fork arrives in order to maintain its grip and block the replication fork.

If the fork is quicker than the Tus rearrangement, it bypasses the block; on the other hand, if there is time for Tus to adjust, the fork is stopped. 

 “We propose that the evolution of different responses to the average rate of different molecular motors could regulate the communication and conflicts among these processes,” explains Hamdan.

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