@article{c98fa5f93d5b41cbb68816ec3cef5aa6,
title = "Genome-wide mapping of human DNA replication by optical replication mapping supports a stochastic model of eukaryotic replication",
abstract = "The heterogeneous nature of eukaryotic replication kinetics and the low efficiency of individual initiation sites make mapping the location and timing of replication initiation in human cells difficult. To address this challenge, we have developed optical replication mapping (ORM), a high-throughput single-molecule approach, and used it to map early-initiation events in human cells. The single-molecule nature of our data and a total of >2,500-fold coverage of the human genome on 27 million fibers averaging ∼300 kb in length allow us to identify initiation sites and their firing probability with high confidence. We find that the distribution of human replication initiation is consistent with inefficient, stochastic activation of heterogeneously distributed potential initiation complexes enriched in accessible chromatin. These observations are consistent with stochastic models of initiation-timing regulation and suggest that stochastic regulation of replication kinetics is a fundamental feature of eukaryotic replication, conserved from yeast to humans.",
author = "Weitao Wang and Klein, {Kyle N.} and Karel Proesmans and Hongbo Yang and Claire Marchal and Xiaopeng Zhu and Tyler Borrman and Alex Hastie and Zhiping Weng and John Bechhoefer and Chen, {Chun Long} and Gilbert, {David M.} and Nicholas Rhind",
note = "Funding Information: We are grateful to Feng Yue for his contribution to the collection of the Bionano data, Jian Ma for help developing the ORM browser, and Peiyao Zhao maintaining the ORM browser server. The work was funded by NIH grants HG010658 , to D.M.G. and GM125872 , to N.R. C.-L.C. was supported by the I. Curie YPI program , the ATIP-Avenir program from CNRS , Plan Cancer from INSERM , the CNRS 80|Prime interdisciplinary program , ANR , and INCa . W.W. was supported by a COFUND IC-3i International PhD fellowship . Funding Information: We are grateful to Feng Yue for his contribution to the collection of the Bionano data, Jian Ma for help developing the ORM browser, and Peiyao Zhao maintaining the ORM browser server. The work was funded by NIH grants HG010658, to D.M.G. and GM125872, to N.R. C.-L.C. was supported by the I. Curie YPI program, the ATIP-Avenir program from CNRS, Plan Cancer from INSERM, the CNRS 80|Prime interdisciplinary program, ANR, and INCa. W.W. was supported by a COFUND IC-3i International PhD fellowship. Conceptualization, C.-L.C. D.M.G. and N.R.; methodology, W.W. K.N.K. K.P. A.H. J.B. C.-L.C. D.M.G. and N.R.; investigation, W.W. K.N.K. K.P. and H.Y.; software, W.W. K.P. C.M. X.Z. and C.-L.C.; validation, W.W. K.N.K. K.P. A.H. H.Y. J.B. C.-L.C. D.M.G. and N.R.; formal analysis, W.W. K.P. J.B. C.-L.C. and N.R.; resources, A.H. C.-L.C. D.M.G. and N.R. data curation, W.W. and C.-L.C. writing ? original draft, N.R.; writing ? review & editing, W.W. K.N.K. K.P. A.H. H.Y. J.B. C.-L.C. D.M.G. and N.R.; visualization, W.W. K.P. C.-L.C. and N.R.; supervision, J.B. C.-L.C. D.M.G. and N.R.; project administration, N.R.; funding acquisition, A.H. C.-L.C. D.M.G. and N.R. A.H. is an employee of Bionano Genomics. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = jul,
day = "15",
doi = "10.1016/j.molcel.2021.05.024",
language = "English (US)",
volume = "81",
pages = "2975--2988.e6",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "14",
}