Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Genome-Wide Identification of Early-Firing Human Replication Origins by Optical Replication Mapping

Kyle Klein, Weitao Wang, Tyler Borrman, Saki Chan, Denghong Zhang, Zhiping Weng, Alex Hastie, Chunlong Chen, David M. Gilbert, Nicholas Rhind
doi: https://doi.org/10.1101/214841
Kyle Klein
1Florida State University, Department of Biological Science, Tallahassee, FL USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Weitao Wang
2Institut Curie, PSL Research University, CNRS, UMR3244, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tyler Borrman
3University of Massachusetts Medical School, Department of Biochemistry and Molecular Pharmacology and Program in Bioinformatics and Integrative Biology, Worcester, MA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Saki Chan
4Bionano Genomics, San Diego, CA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Denghong Zhang
4Bionano Genomics, San Diego, CA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhiping Weng
3University of Massachusetts Medical School, Department of Biochemistry and Molecular Pharmacology and Program in Bioinformatics and Integrative Biology, Worcester, MA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alex Hastie
4Bionano Genomics, San Diego, CA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chunlong Chen
2Institut Curie, PSL Research University, CNRS, UMR3244, Paris, France
5Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR3244, Paris, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David M. Gilbert
1Florida State University, Department of Biological Science, Tallahassee, FL USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicholas Rhind
3University of Massachusetts Medical School, Department of Biochemistry and Molecular Pharmacology and Program in Bioinformatics and Integrative Biology, Worcester, MA USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The timing of DNA replication is largely regulated by the location and timing of replication origin firing. Therefore, much effort has been invested in identifying and analyzing human replication origins. However, the heterogeneous nature of eukaryotic replication kinetics and the low efficiency of individual origins in metazoans has made mapping the location and timing of replication initiation in human cells difficult. We have mapped early-firing origins in HeLa cells using Optical Replication Mapping, a high-throughput single-molecule approach based on Bionano Genomics genomic mapping technology. The single-molecule nature and 290-fold coverage of our dataset allowed us to identify origins that fire with as little as 1% efficiency. We find sites of human replication initiation in early S phase are not confined to well-defined efficient replication origins, but are instead distributed across broad initiation zones consisting of many inefficient origins. These early-firing initiation zones co-localize with initiation zones inferred from Okazaki-fragment-mapping analysis and are enriched in ORC1 binding sites. Although most early-firing origins fire in early-replication regions of the genome, a significant number fire in late-replicating regions, suggesting that the major difference between origins in early and late replicating regions is their probability of firing in early S-phase, as opposed to qualitative differences in their firing-time distributions. This observation is consistent with stochastic models of origin timing regulation, which explain the regulation of replication timing in yeast.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted November 06, 2017.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genome-Wide Identification of Early-Firing Human Replication Origins by Optical Replication Mapping
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genome-Wide Identification of Early-Firing Human Replication Origins by Optical Replication Mapping
Kyle Klein, Weitao Wang, Tyler Borrman, Saki Chan, Denghong Zhang, Zhiping Weng, Alex Hastie, Chunlong Chen, David M. Gilbert, Nicholas Rhind
bioRxiv 214841; doi: https://doi.org/10.1101/214841
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Genome-Wide Identification of Early-Firing Human Replication Origins by Optical Replication Mapping
Kyle Klein, Weitao Wang, Tyler Borrman, Saki Chan, Denghong Zhang, Zhiping Weng, Alex Hastie, Chunlong Chen, David M. Gilbert, Nicholas Rhind
bioRxiv 214841; doi: https://doi.org/10.1101/214841

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8766)
  • Bioengineering (6480)
  • Bioinformatics (23346)
  • Biophysics (11751)
  • Cancer Biology (9149)
  • Cell Biology (13255)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15088)
  • Genetics (10402)
  • Genomics (14011)
  • Immunology (9122)
  • Microbiology (22050)
  • Molecular Biology (8780)
  • Neuroscience (47373)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2209)
  • Systems Biology (6016)
  • Zoology (1250)