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  Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription

Brambati, A., Zardoni, L., Achar, Y. J., Piccini, D., Galanti, L., Colosio, A., et al. (2018). Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription. Nucleic Acids Research, 46(3), 1227-1239. doi:10.1093/nar/gkx945.

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© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
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 Creators:
Brambati, Alessandra1, Author
Zardoni, Luca1, Author
Achar, Yathish Jagadheesh1, Author
Piccini, Daniele1, Author
Galanti, Lorenzo2, Author              
Colosio, Arianna1, Author
Foiani, Marco1, Author
Liberi, Giordano1, Author
Affiliations:
1external, ou_persistent22              
2Pfander, Boris / DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565165              

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Free keywords: ONCOGENE-INDUCED SENESCENCE; EUKARYOTIC DNA-REPLICATION; MAINTAIN GENOME STABILITY; DAMAGE RESPONSE; FRAGILE SITES; PAUSE SITES; HUMAN-CELLS; R-LOOPS; STRESS; YEASTBiochemistry & Molecular Biology;
 Abstract: The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of replication forks encountering transcription by removing RNA-DNA hybrids. Here we show that, in sen1 mutants, when a replication fork clashes head-on with transcription is arrested and, as a consequence, the progression of the sister fork moving in the opposite direction within the same replicon is also impaired. Therefore, sister forks remain coupled when one of the two forks is arrested by transcription, a fate different from that experienced by forks encountering Double Strand Breaks. We also show that dormant origins of replication are activated to ensure DNA synthesis in the proximity to the forks arrested by transcription. Dormant origin firing is not inhibited by the replication checkpoint, rather dormant origins are fired if they cannot be timely inactivated by passive replication. In sen1 mutants, the Mre11 and Mrc1-Ctf4 complexes protect the forks arrested by transcription from processing mediated by the Exo1 nuclease. Thus, a harmless head-on replication-transcription clash resolution requires the fine-tuning of origin firing and coordination among Sen1, Exo1, Mre11 and Mrc1-Ctf4 complexes.

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Language(s): eng - English
 Dates: 2017-10-202018-02-16
 Publication Status: Published in print
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000425294400023
DOI: 10.1093/nar/gkx945
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Title: Nucleic Acids Research
  Other : Nucleic Acids Res.
Source Genre: Journal
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Publ. Info: Oxford Acad
Pages: - Volume / Issue: 46 (3) Sequence Number: - Start / End Page: 1227 - 1239 Identifier: ISSN: 0301-5610
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000262810