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J Biol Chem. 2010 Dec 17;285(51):40004-11. doi: 10.1074/jbc.M110.148924. Epub 2010 Oct 20.

Relicensing of transcriptionally inactivated replication origins in budding yeast.

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Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.


DNA replication origins are licensed in early G(1) phase of the cell cycle where the origin recognition complex (ORC) recruits the minichromosome maintenance (MCM) helicase to origins. These pre-replicative complexes (pre-RCs) remain inactive until replication is initiated in the S phase. However, transcriptional activity in the regions of origins can eliminate their functionality by displacing the components of pre-RC from DNA. We analyzed genome-wide data of mRNA and cryptic unstable transcripts in the context of locations of replication origins in yeast genome and found that at least one-third of the origins are transcribed and therefore might be inactivated by transcription. When investigating the fate of transcriptionally inactivated origins, we found that replication origins were repetitively licensed in G(1) to reestablish their functionality after transcription. We propose that reloading of pre-RC components in G(1) might be utilized for the maintenance of sufficient number of competent origins for efficient initiation of DNA replication in S phase.

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