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Review
. 2013 Feb 20;32(4):493-5.
doi: 10.1038/emboj.2013.20. Epub 2013 Feb 1.

Early replication fragile sites: where replication-transcription collisions cause genetic instability

Oliver Mortusewicz  1 , Patrick Herr, Thomas Helleday
Affiliations
Review

Early replication fragile sites: where replication-transcription collisions cause genetic instability

Oliver Mortusewicz et al. EMBO J. .

Abstract

Cell (2013) 152: 620–632 doi:; DOI: 10.1016/j.cell.2013.01.006; published online January 31 2013

Although it is known that replication stress causes genetic instability, the underlying mechanisms are not yet fully understood. A new study by Barlow et al (2013) used an elegant genome-wide chromatin immunoprecipitation approach to reveal that DNA lesions induced by replication stress occur predominantly in early replicating and actively transcribed gene clusters. These ‘early replication fragile sites’ (ERFS) can be the source for rearrangements commonly found in cancer, and represent a new type of fragile site, distinct from common fragile sites (CFS).

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Comparison of CFS with the newly identified ERFS. Oncogene-induced replication stress causes replication fork stalling and collapse at both CFS and ERFS; ATR kinase and homologous recombination prevent collapse and mediate fork restart and repair. Arrows and coloured DNA sequences indicate actively transcribed genes and blue arrowheads denote progressing replication forks.
See this image and copyright information in PMC

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