Replication Termination at Eukaryotic Chromosomes Is Mediated by Top2 and Occurs at Genomic Loci Containing Pausing Elements

Daniele Fachinetti, Rodrigo Bermejo, Andrea Cocito, Simone Minardi, Yuki Katou, Yutaka Kanoh, Katsuhiko Shirahige, Anna Azvolinsky, Virginia A. Zakian, Marco Foiani

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Chromosome replication initiates at multiple replicons and terminates when forks converge. In E. coli, the Tus-TER complex mediates polar fork converging at the terminator region, and aberrant termination events challenge chromosome integrity and segregation. Since in eukaryotes, termination is less characterized, we used budding yeast to identify the factors assisting fork fusion at replicating chromosomes. Using genomic and mechanistic studies, we have identified and characterized 71 chromosomal termination regions (TERs). TERs contain fork pausing elements that influence fork progression and merging. The Rrm3 DNA helicase assists fork progression across TERs, counteracting the accumulation of X-shaped structures. The Top2 DNA topoisomerase associates at TERs in S phase, and G2/M facilitates fork fusion and prevents DNA breaks and genome rearrangements at TERs. We propose that in eukaryotes, replication fork barriers, Rrm3, and Top2 coordinate replication fork progression and fusion at TERs, thus counteracting abnormal genomic transitions.

Original languageEnglish (US)
Pages (from-to)595-605
Number of pages11
JournalMolecular Cell
Volume39
Issue number4
DOIs
StatePublished - Aug 2010

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • DNA

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    Fachinetti, D., Bermejo, R., Cocito, A., Minardi, S., Katou, Y., Kanoh, Y., Shirahige, K., Azvolinsky, A., Zakian, V. A., & Foiani, M. (2010). Replication Termination at Eukaryotic Chromosomes Is Mediated by Top2 and Occurs at Genomic Loci Containing Pausing Elements. Molecular Cell, 39(4), 595-605. https://doi.org/10.1016/j.molcel.2010.07.024