Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements.
Publication Year
2010
Type
Journal Article
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.
Keywords
Nucleic Acid Conformation,
Mutation,
DNA-Binding Proteins,
Cell Division,
Saccharomyces cerevisiae Proteins,
Saccharomyces cerevisiae,
DNA Replication,
S Phase,
Genetic Loci,
Terminator Regions, Genetic,
Gene Rearrangement,
G2 Phase,
DNA Helicases,
DNA, Fungal,
DNA Breaks,
Antigens, Neoplasm,
Chromosome Fragility,
Chromosomes, Fungal,
DNA Topoisomerases, Type II
Journal
Mol Cell
Volume
39
Issue
4
Pages
595-605
Date Published
08/2010
ISSN Number
1097-4164
Alternate Journal
Mol. Cell
PMID
20797631