Avoiding chromosome pathology when replication forks collide
| Autor: | Christian J. Rudolph, Amy L. Upton, Anna Stockum, Conrad A. Nieduszynski, Robert G. Lloyd |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Genomic instability
DNA Replication DNA Bacterial Exonucleases Genetic Markers Genome instability Exodeoxyribonuclease V DNA Single-Stranded Replication Origin DNA Exonuclease Biology Chromosomes Article Genomic Instability Fork (software development) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Bacterial Proteins Gene duplication Escherichia coli Bacteriophages 030304 developmental biology Genetics 0303 health sciences Multidisciplinary DNA synthesis Escherichia coli Proteins DNA Helicases DNA replication Chromosomes Bacterial Origin firing DNA-Binding Proteins chemistry Replication Initiation Replisome DNA Circular 030217 neurology & neurosurgery DNA |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature12312 |
| Popis: | This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Macmillan Publishers Limited. Chromosome duplication normally initiates through the assembly of replication fork complexes at defined origins1, 2. DNA synthesis by any one fork is thought to cease when it meets another travelling in the opposite direction, at which stage the replication machinery may simply dissociate before the nascent strands are finally ligated. But what actually happens is not clear. Here we present evidence consistent with the idea that every fork collision has the potential to threaten genomic integrity. In Escherichia coli this threat is kept at bay by RecG DNA translocase3 and by single-strand DNA exonucleases. Without RecG, replication initiates where forks meet through a replisome assembly mechanism normally associated with fork repair, replication restart and recombination4, 5, establishing new forks with the potential to sustain cell growth and division without an active origin. This potential is realized when roadblocks to fork progression are reduced or eliminated. It relies on the chromosome being circular, reinforcing the idea that replication initiation is triggered repeatedly by fork collision. The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit several origins to replicate each chromosome. THe MRC, the Leverhulme Trust, and the BBSRC. |
| Databáze: | OpenAIRE |
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