IMR Press / FBL / Volume 10 / Issue 1 / DOI: 10.2741/1564

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Critical role of R-loops in processing replication blocks
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1 The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle, WA 98195-7705, USA
Front. Biosci. (Landmark Ed) 2005, 10(1), 689–698;
Published: 1 January 2005

Blocks in replication result from impediments to the advancing replication machinery and are lethal if not resolved. The replication fork must be reassembled for DNA synthesis to proceed. Fork assembly outside the chromosomal origin of replication (oriC) is mediated by recombination or via a helicase-dependent pathway. ColE1 plasmid origins of replication and oriK sites initiate primosome assembly by an RNA-DNA hybrid structure known as R-loop. We review evidence suggesting that R-loops are frequent during normal cell growth and that R-loops are critical for the maintenance of genome integrity. We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed. Unlike recombination and helicase-dependent fork restoration, this mechanism would operate preferentially in transcribed areas of the genome, which are known to be particularly susceptible to DNA damage. Our model emphasizes the intimate relationship between transcription and repair, offers a unifying interpretation of phenotypes attributed to bacterial strains deficient in R-loop fork assembly, and calls for a renewed focus on R-loop formation and regulation.

DNA repair
Replication block
Pol I
Stable DNA replication
transcription-coupled repair
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