TY - JOUR
T1 - Replication Termination at Eukaryotic Chromosomes Is Mediated by Top2 and Occurs at Genomic Loci Containing Pausing Elements
AU - Fachinetti, Daniele
AU - Bermejo, Rodrigo
AU - Cocito, Andrea
AU - Minardi, Simone
AU - Katou, Yuki
AU - Kanoh, Yutaka
AU - Shirahige, Katsuhiko
AU - Azvolinsky, Anna
AU - Zakian, Virginia A.
AU - Foiani, Marco
N1 - Funding Information:
We thank A. Verreault and E. Schwob for reagents; Ted Weinert for communicating unpublished results; D. Branzei, M. Lopes, and Y. Doksani for suggestions and critical reading of the manuscript; and all members of our laboratories for discussions. We thank M. Cesaroni for TER sequence analysis, M. Saponaro for technical advice, and F. Ciccarelli for suggestion on evolution analysis. Work in the M.F. laboratory is supported by grants from Italian Association for Cancer Research, Italian Foundation for Cancer Research, Telethon-Italy, European Community, and Italian Ministry of Health. D.F. was supported by an AIRC fellowship. Work in K.S.'s laboratory is supported by a grant of the Genome Network Project and Grant-in-Aid for Scientific Research (S) from the MEXT, Japan. Y. Katou is a GCOE research associate. Work in V.A.Z.'s laboratory is supported by NIH grant R37 029638.
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - DNA
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U2 - 10.1016/j.molcel.2010.07.024
DO - 10.1016/j.molcel.2010.07.024
M3 - Article
C2 - 20797631
AN - SCOPUS:77955997707
SN - 1097-2765
VL - 39
SP - 595
EP - 605
JO - Molecular Cell
JF - Molecular Cell
IS - 4
ER -