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Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts

During S phase, the entire genome must be precisely duplicated, with no sections of DNA left unreplicated. Here, we develop a simple mathematical model to describe the probability of replication failing due to the irreversible stalling of replication forks. We show that the probability of complete g...

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Autores principales: Newman, Timothy J., Mamun, Mohammed A., Nieduszynski, Conrad A., Blow, J. Julian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834809/
https://www.ncbi.nlm.nih.gov/pubmed/23963700
http://dx.doi.org/10.1093/nar/gkt728
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author Newman, Timothy J.
Mamun, Mohammed A.
Nieduszynski, Conrad A.
Blow, J. Julian
author_facet Newman, Timothy J.
Mamun, Mohammed A.
Nieduszynski, Conrad A.
Blow, J. Julian
author_sort Newman, Timothy J.
collection PubMed
description During S phase, the entire genome must be precisely duplicated, with no sections of DNA left unreplicated. Here, we develop a simple mathematical model to describe the probability of replication failing due to the irreversible stalling of replication forks. We show that the probability of complete genome replication is maximized if replication origins are evenly spaced, the largest inter-origin distances are minimized, and the end-most origins are positioned close to chromosome ends. We show that origin positions in the yeast Saccharomyces cerevisiae genome conform to all three predictions thereby maximizing the probability of complete replication if replication forks stall. Origin positions in four other yeasts—Kluyveromyces lactis, Lachancea kluyveri, Lachancea waltii and Schizosaccharomyces pombe—also conform to these predictions. Equating failure rates at chromosome ends with those in chromosome interiors gives a mean per nucleotide fork stall rate of ∼5 × 10(−8), which is consistent with experimental estimates. Using this value in our theoretical predictions gives replication failure rates that are consistent with data from replication origin knockout experiments. Our theory also predicts that significantly larger genomes, such as those of mammals, will experience a much greater probability of replication failure genome-wide, and therefore will likely require additional compensatory mechanisms.
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spelling pubmed-38348092013-11-21 Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts Newman, Timothy J. Mamun, Mohammed A. Nieduszynski, Conrad A. Blow, J. Julian Nucleic Acids Res Genome Integrity, Repair and Replication During S phase, the entire genome must be precisely duplicated, with no sections of DNA left unreplicated. Here, we develop a simple mathematical model to describe the probability of replication failing due to the irreversible stalling of replication forks. We show that the probability of complete genome replication is maximized if replication origins are evenly spaced, the largest inter-origin distances are minimized, and the end-most origins are positioned close to chromosome ends. We show that origin positions in the yeast Saccharomyces cerevisiae genome conform to all three predictions thereby maximizing the probability of complete replication if replication forks stall. Origin positions in four other yeasts—Kluyveromyces lactis, Lachancea kluyveri, Lachancea waltii and Schizosaccharomyces pombe—also conform to these predictions. Equating failure rates at chromosome ends with those in chromosome interiors gives a mean per nucleotide fork stall rate of ∼5 × 10(−8), which is consistent with experimental estimates. Using this value in our theoretical predictions gives replication failure rates that are consistent with data from replication origin knockout experiments. Our theory also predicts that significantly larger genomes, such as those of mammals, will experience a much greater probability of replication failure genome-wide, and therefore will likely require additional compensatory mechanisms. Oxford University Press 2013-11 2013-08-19 /pmc/articles/PMC3834809/ /pubmed/23963700 http://dx.doi.org/10.1093/nar/gkt728 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genome Integrity, Repair and Replication
Newman, Timothy J.
Mamun, Mohammed A.
Nieduszynski, Conrad A.
Blow, J. Julian
Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts
title Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts
title_full Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts
title_fullStr Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts
title_full_unstemmed Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts
title_short Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts
title_sort replisome stall events have shaped the distribution of replication origins in the genomes of yeasts
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834809/
https://www.ncbi.nlm.nih.gov/pubmed/23963700
http://dx.doi.org/10.1093/nar/gkt728
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