Transcription-replication conflicts at chromosomal fragile sites—consequences in M phase and beyond
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Collision between the molecular machineries responsible for transcription and replication is an important source of genome instability. Certain transcribed regions known as chromosomal fragile sites are particularly prone to recombine and mutate in a manner that correlates with specific transcription and replication patterns. At the same time, these chromosomal fragile sites engage in aberrant DNA structures in mitosis. Here, we discuss the mechanistic details of transcription–replication conflicts including putative scenarios for R-loop-induced replication inhibition to understand how transcription–replication conflicts transition from S phase into various aberrant DNA structures in mitosis.
KeywordsChromosomal fragile sites Transcription Replication Template switching Mitosis Anaphase bridges
This work was supported by The Danish Agency for Science, Technology and Innovation and the Villum Foundation. We thank Valeria Naim, Xin Shao, Vasileios Voutsinos, and Jakob Nilsson for comments on the manuscript.
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Conflict of interest
The authors declare that they have no competing interests.
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This article does not contain any studies with human participant or animals performed by any of the authors.
- Balakrishnan L, Bambara RA (2013b) Okazaki fragment metabolism. Cold Spring Harbor perspectives in biology 5Google Scholar
- Blower MD (2016) Centromeric transcription regulates Aurora-B localization and activation. Cell RepGoogle Scholar
- Kim N, Jinks-Robertson S (2012) Transcription as a source of genome instability. Nat Rev 13:204–214Google Scholar