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Non‐Canonical Replication Initiation: You’re Fired!

Nature Research Centre, Akademijos g. 2, LT‐08412 Vilnius, Lithuania
CABIMER‐Universidad de Sevilla, Avd Americo Vespucio sn, 41092 Sevilla, Spain
Author to whom correspondence should be addressed.
Genes 2017, 8(2), 54;
Received: 10 November 2016 / Accepted: 19 January 2017 / Published: 27 January 2017
(This article belongs to the Special Issue DNA Replication Controls)
PDF [618 KB, uploaded 3 February 2017]


The division of prokaryotic and eukaryotic cells produces two cells that inherit a perfect copy of the genetic material originally derived from the mother cell. The initiation of canonical DNA replication must be coordinated to the cell cycle to ensure the accuracy of genome duplication. Controlled replication initiation depends on a complex interplay of cis‐acting DNA sequences, the so‐called origins of replication (ori), with trans‐acting factors involved in the onset of DNA synthesis. The interplay of cis‐acting elements and trans‐acting factors ensures that cells initiate replication at sequence‐specific sites only once, and in a timely order, to avoid chromosomal endoreplication. However, chromosome breakage and excessive RNA:DNA hybrid formation can cause breakinduced (BIR) or transcription‐initiated replication (TIR), respectively. These non‐canonical replication events are expected to affect eukaryotic genome function and maintenance, and could be important for genome evolution and disease development. In this review, we describe the difference between canonical and non‐canonical DNA replication, and focus on mechanistic differences and common features between BIR and TIR. Finally, we discuss open issues on the factors and molecular mechanisms involved in TIR. View Full-Text
Keywords: replication control; RNA:DNA hybrid; transcription‐initiated replication replication control; RNA:DNA hybrid; transcription‐initiated replication

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Ravoitytė, B.; Wellinger, R.E. Non‐Canonical Replication Initiation: You’re Fired! Genes 2017, 8, 54.

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