Transcription-replication conflicts at chromosomal fragile sites—consequences in M phase and beyond

Abstract

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.

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Acknowledgments

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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Correspondence to Vibe H. Oestergaard or Michael Lisby.

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Oestergaard, V.H., Lisby, M. Transcription-replication conflicts at chromosomal fragile sites—consequences in M phase and beyond. Chromosoma 126, 213–222 (2017). https://doi.org/10.1007/s00412-016-0617-2

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Keywords

  • Chromosomal fragile sites
  • Transcription
  • Replication
  • Template switching
  • Mitosis
  • Anaphase bridges