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

PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells

Laura J. Bailey, Julie Bianchi, View ORCID ProfileAidan J. Doherty
doi: https://doi.org/10.1101/501304
Laura J. Bailey
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9RQ, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julie Bianchi
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9RQ, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aidan J. Doherty
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9RQ, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Aidan J. Doherty
  • For correspondence: AJD21@sussex.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Eukaryotic Primase-Polymerase (PrimPol) is an enzyme that maintains efficient DNA duplication by repriming replication restart downstream of replicase stalling lesions and structures. To elucidate the cellular requirements for PrimPol in human cells, we generated PrimPol-deleted cell lines and show that it plays key roles in maintaining active replication in both the nucleus and mitochondrion, even in the absence of exogenous damage. Human cells lacking PrimPol exhibit delayed recovery after UV-C damage and increased mutation rates, micronuclei and sister chromatin exchanges but are not sensitive to genotoxins. PrimPol is also required during mitochondrial replication, with PrimPol-deficient cells having increased mtDNA copy number but displaying a significant decrease in replication rates. Deletion of PrimPol in XPV cells, lacking functional Pol Eta, causes an increase in DNA damage sensitivity and pronounced fork stalling after UV-C treatment. We show that, unlike canonical TLS polymerases, PrimPol is important for allowing active replication to proceed, even in the absence of exogenous damage, thus preventing the accumulation of excessive fork stalling and genetic mutations. Together, these findings highlight the importance of PrimPol for maintaining efficient DNA replication in unperturbed cells and its complementary roles, with Pol Eta, in damage tolerance in human cells.

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 4.0 International license.
Back to top
PreviousNext
Posted December 19, 2018.
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.
PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells
(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
PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells
Laura J. Bailey, Julie Bianchi, Aidan J. Doherty
bioRxiv 501304; doi: https://doi.org/10.1101/501304
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
PrimPol is required for the maintenance of efficient nuclear and mitochondrial DNA replication in human cells
Laura J. Bailey, Julie Bianchi, Aidan J. Doherty
bioRxiv 501304; doi: https://doi.org/10.1101/501304

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

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3579)
  • Biochemistry (7525)
  • Bioengineering (5486)
  • Bioinformatics (20702)
  • Biophysics (10261)
  • Cancer Biology (7939)
  • Cell Biology (11585)
  • Clinical Trials (138)
  • Developmental Biology (6573)
  • Ecology (10145)
  • Epidemiology (2065)
  • Evolutionary Biology (13553)
  • Genetics (9502)
  • Genomics (12794)
  • Immunology (7888)
  • Microbiology (19459)
  • Molecular Biology (7618)
  • Neuroscience (41916)
  • Paleontology (307)
  • Pathology (1253)
  • Pharmacology and Toxicology (2182)
  • Physiology (3253)
  • Plant Biology (7010)
  • Scientific Communication and Education (1291)
  • Synthetic Biology (1942)
  • Systems Biology (5410)
  • Zoology (1108)