What is it about?
In this review, we examine how DNA replication and transcription can interfere with each other when the DNA-copying machinery and RNA polymerase share the same DNA template. We focus mainly on bacterial systems such as Escherichia coli, while also drawing comparisons with eukaryotic cells. We highlight evidence that RNA polymerase complexes, especially those stalled at DNA damage or stuck after backtracking, can obstruct replication forks, the moving structures that copy DNA. We also discuss how cells reduce these conflicts through chromosome organisation, RNA polymerase modulators such as GreA, GreB, DksA and Mfd, transcription-coupled repair, and pathways that restart or repair blocked replication forks.
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Why is it important?
Genome duplication has to happen while genes are being expressed, so even rare conflicts between replication and transcription may matter for genome stability and cell viability. This review helps bring together evidence that cells avoid these conflicts at several levels, from the orientation of genes to the removal of stalled RNA polymerase complexes. It also supports a cautious view: the systems that prevent conflict are so well tuned that direct evidence for some outcomes, such as replisome dissociation after collision, remains difficult to obtain.
Perspectives
What stands out to us is the idea that transcription factors usually discussed in the context of gene expression may also help protect DNA replication. We were interested in connecting bacterial genetics, in vitro studies, chromosome organisation and eukaryotic examples into one picture of how cells keep two essential processes from obstructing each other. The review also emphasises an important experimental point: to see these conflicts clearly, it may be necessary to study cells in which one or more protective systems has been disrupted.
Dr. Christian J Rudolph
Brunel University
Read the Original
This page is a summary of: Avoiding and resolving conflicts between DNA replication and transcription, DNA Repair, July 2007, Elsevier,
DOI: 10.1016/j.dnarep.2007.02.017.
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