umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. (Andrei Chabes)
Show others and affiliations
2017 (English)In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 68, no 2, p. 446-455Article in journal (Refereed) Published
Abstract [en]

The checkpoint kinase Rad53 is activated during replication stress to prevent fork collapse, an essential but poorly understood process. Here we show that Rad53 couples leading- and lagging-strand synthesis under replication stress. In rad53-1 cells stressed by dNTP depletion, the replicative DNA helicase, MCM, and the leading-strand DNA polymerase, Pol ε, move beyond the site of DNA synthesis, likely unwinding template DNA. Remarkably, DNA synthesis progresses further along the lagging strand than the leading strand, resulting in the exposure of long stretches of single-stranded leading-strand template. The asymmetric DNA synthesis in rad53-1 cells is suppressed by elevated levels of dNTPs in vivo, and the activity of Pol ε is compromised more than lagging-strand polymerase Pol δ at low dNTP concentrations in vitro. Therefore, we propose that Rad53 prevents the generation of excessive ssDNA under replication stress by coordinating DNA unwinding with synthesis of both strands.

Place, publisher, year, edition, pages
Elsevier, 2017. Vol. 68, no 2, p. 446-455
Keywords [en]
ChIP-ssSeq, DNA replication checkpoint, Rad53, dNTP pools, eSPAN, fork collapse, lagging strand DNA synthesis, leading strand DNA synthesis
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-140697DOI: 10.1016/j.molcel.2017.09.018ISI: 000413239400017PubMedID: 29033319OAI: oai:DiVA.org:umu-140697DiVA, id: diva2:1149943
Available from: 2017-10-17 Created: 2017-10-17 Last updated: 2018-06-09Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Sharma, SushmaChabes, Andrei

Search in DiVA

By author/editor
Sharma, SushmaChabes, Andrei
By organisation
Department of Medical Biochemistry and Biophysics
In the same journal
Molecular Cell
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 103 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf