Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements.
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.
Fachinetti
Daniele
D
Fondazione IFOM, Istituto FIRC di Oncologia Molecolare (IFOM-IEO Campus), Via Adamello 16, 20139 Milan, Italy.
Bermejo
Rodrigo
R
Cocito
Andrea
A
Minardi
Simone
S
Katou
Yuki
Y
Kanoh
Yutaka
Y
Shirahige
Katsuhiko
K
Azvolinsky
Anna
A
Zakian
Virginia A
VA
Foiani
Marco
M
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002873:Chromosome Fragility; D015825:Chromosomes, Fungal; D053960:DNA Breaks; D004265:DNA Helicases / Q000378:metabolism; D004261:DNA Replication; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000096:biosynthesis* / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase; D015321:Gene Rearrangement; D056426:Genetic Loci; D009154:Mutation; D009690:Nucleic Acid Conformation; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013728:Terminator Regions, Genetic
D000951:Antigens, Neoplasm; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C459081:Rrm3 protein, S cerevisiae; D004265:DNA Helicases; D004250:DNA Topoisomerases, Type II
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