Transcription and replication

Abstract

Replication and transcription machineries progress at high speed on the same DNA template, which inevitably causes traffic accidents. Problems are not only caused by frontal collisions between polymerases, but also by cotranscriptional R-loops. These RNA-DNA hybrids induce genomic instability by blocking fork progression and could be implicated in the development of cancer.

Acknowledgements

We thank Armelle Lengronne and members of the PP laboratory for discussions and critical reading of the manuscript. A.M.P. was supported by an FRM post-doctoral fellowship. M.L.C. thanks Inserm for fellowship. Work in the P.P. laboratory is supported by FRM (Equipe FRM), ANR, INCa and the EMBO Young Investigator Programme.

Figures and Tables

Figure 1 Models for interference between DNA replication and transcription. (A) The head-on collision model stipulates that a direct clash between the replisome and the RNA polymerase causes fork stalling, dissociation of the replisome and/or formation of recombinogenic reversed fork. This model implies that DNA replication and transcription occur simultaneously on the same DNA template. (B) In the cotranscriptional R-loops model, RNA-DNA hybrids formed during transcription interfere with replication fork progression and induce TAR. It is not clear whether fork arrest and recombination are caused by the DNA-RNA hybrid itself or by DNA lesions accumulating on the exposed ssDNA strand (diamonds).

Figure 2 Schematic representation of the replication fork barrier at the S. cerevisiae rDNA array. This array is composed of ∼200 identical repeats (9.1 kb) containing a large 35S rRNA gene, a small 5S rRNA gene and a replication origin (ARS). Replication forks progressing opposite to the direction of 35S transcription are arrested at the replication fork barrier (RFB). P: Promoter of the 35S gene. E/T, enhancer/terminator.