Stochasticity of replication forks' speeds plays a key role in the dynamics of DNA replication.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
12
06
2019
accepted:
29
10
2019
revised:
22
01
2020
pubmed:
24
12
2019
medline:
17
3
2020
entrez:
24
12
2019
Statut:
epublish
Résumé
Eukaryotic DNA replication is elaborately orchestrated to duplicate the genome timely and faithfully. Replication initiates at multiple origins from which replication forks emanate and travel bi-directionally. The complex spatio-temporal regulation of DNA replication remains incompletely understood. To study it, computational models of DNA replication have been developed in S. cerevisiae. However, in spite of the experimental evidence of forks' speed stochasticity, all models assumed that forks' speeds are the same. Here, we present the first model of DNA replication assuming that speeds vary stochastically between forks. Utilizing data from both wild-type and hydroxyurea-treated yeast cells, we show that our model is more accurate than models assuming constant forks' speed and reconstructs dynamics of DNA replication faithfully starting both from population-wide data and data reflecting fork movement in individual cells. Completion of replication in a timely manner is a challenge due to its stochasticity; we propose an empirically derived modification to replication speed based on the distance to the approaching fork, which promotes timely completion of replication. In summary, our work discovers a key role that stochasticity of the forks' speed plays in the dynamics of DNA replication. We show that without including stochasticity of forks' speed it is not possible to accurately reconstruct movement of individual replication forks, measured by DNA combing.
Identifiants
pubmed: 31869320
doi: 10.1371/journal.pcbi.1007519
pii: PCOMPBIOL-D-19-00948
pmc: PMC6975548
doi:
Substances chimiques
DNA, Fungal
0
Hydroxyurea
X6Q56QN5QC
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007519Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM112131
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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