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

被引：126

作者：

Fachinetti, Daniele ^{[1
,2
]}

Bermejo, Rodrigo ^{[1
,2
]}

Cocito, Andrea ^{[1
]}

Minardi, Simone ^{[3
]}

Katou, Yuki ^{[4
]}

Kanoh, Yutaka ^{[4
]}

Shirahige, Katsuhiko ^{[4
]}

Azvolinsky, Anna ^{[5
]}

Zakian, Virginia A. ^{[5
]}

Foiani, Marco ^{[1
,2
]}

机构：

[1] Ist FIRC Oncol Mol IFOM IEO Campus, Fdn IFOM, I-20139 Milan, Italy

[2] Univ Milan, DSBB, I-20133 Milan, Italy

[3] COGENTECH Consortium Genom Technol, I-20139 Milan, Italy

[4] Tokyo Inst Technol, Yokohama, Kanagawa 2268501, Japan

[5] Princeton Univ, Princeton, NJ 08544 USA

来源：

MOLECULAR CELL | 2010年 / 39卷 / 04期

关键词：

DNA TOPOISOMERASE-II; SACCHAROMYCES-CEREVISIAE; FORK PROGRESSION; BUDDING YEAST; DAMAGE RESPONSE; FRAGILE SITE; 3' END; TRANSCRIPTION; HELICASE; ORIGINS;

D O I：

10.1016/j.molcel.2010.07.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：595 / 605

页数：11

共 53 条

[1] Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast [J].