DOI: 10.1101/gad.1252304. Idling by DNA polymerase δ maintains a ligatable nick during lagging-strand DNA replication

Idling by DNA polymerase δ maintains a ligatable nick during lagging-strand DNA replication

10.1101/gad.1252304

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

During each yeast cell cycle, ∼100,000 nicks are generated during lagging-strand DNA replication. Efficient nick processing during Okazaki fragment maturation requires the coordinated action of DNA polymerase δ (Pol δ) and the FLAP endonuclease FEN1. Misregulation of this process leads to the accumulation of double-stranded breaks and cell lethality. Our studies highlight a remarkably efficient mechanism for Okazaki fragment maturation in which Pol δ by default displaces 2–3 nt of any downstream RNA or DNA it encounters. In the presence of FEN1, efficient nick translation ensues, whereby a mixture of mono- and small oligonucleotides are released. If FEN1 is absent or not optimally functional, the ability of Pol δ to back up via its 3′–5′-exonuclease activity, a process called idling, maintains the polymerase at a position that is ideal either for ligation (in case of a DNA–DNA nick) or for subsequent engagement by FEN1 (in case of a DNA–RNA nick). Consistent with the hypothesis that DNA polymerase ϵ is the leading-strand enzyme, we observed no idling by this enzyme and no cooperation with FEN1 for creating a ligatable nick.

Bibliography

Garg, P., Stith, C. M., Sabouri, N., Johansson, E., & Burgers, P. M. (2004). Idling by DNA polymerase Î´ maintains a ligatable nick during lagging-strand DNA replication. Genes & Development, 18(22), 2764â2773.

Authors 5

Parie Garg (first)
Carrie M. Stith (additional)
Nasim Sabouri (additional)
Erik Johansson (additional)
Peter M. Burgers (additional)

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Dates

Type	When
Created	20 years, 10 months ago (Nov. 2, 2004, 9:58 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 10:23 a.m.)
Indexed	11 months ago (Oct. 5, 2024, 8:32 p.m.)
Issued	20 years, 10 months ago (Nov. 1, 2004)
Published	20 years, 10 months ago (Nov. 1, 2004)
Published Online	20 years, 10 months ago (Nov. 1, 2004)
Published Print	20 years, 9 months ago (Nov. 15, 2004)

Funders 0

None

BibTeX

@article{Garg_2004, title={Idling by DNA polymerase δ maintains a ligatable nick during lagging-strand DNA replication}, volume={18}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1252304}, DOI={10.1101/gad.1252304}, number={22}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Garg, Parie and Stith, Carrie M. and Sabouri, Nasim and Johansson, Erik and Burgers, Peter M.}, year={2004}, month=nov, pages={2764–2773} }

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