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.

Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements / D. Fachinetti, R. Bermejo, A. Cocito, S. Minardi, Y. Katou, Y. Kanoh, K. Shirahige, A. Azvolinsky, V.A. Zakian, M. Foiani. - In: MOLECULAR CELL. - ISSN 1097-2765. - 39:4(2010 Aug 27), pp. 595-605. [10.1016/j.molcel.2010.07.024]

Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements

D. Fachinetti
Primo
;
M. Foiani
Ultimo
2010-08-27

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.
DNA, Fungal; Genetic Loci; DNA Breaks; DNA Topoisomerases, Type II; DNA-Binding Proteins; Saccharomyces cerevisiae Proteins; S Phase; Gene Rearrangement; Antigens, Neoplasm; Nucleic Acid Conformation; Saccharomyces cerevisiae; Chromosomes, Fungal; Terminator Regions, Genetic; DNA Helicases; Chromosome Fragility; G2 Phase; Mutation; DNA Replication; Cell Division
Settore BIO/11 - Biologia Molecolare
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/658678
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