Evidence map›Paper›PMID 33555053›Full record

ArticleThe EMBO journal2021

The eukaryotic replisome tolerates leading-strand base damage by replicase switching.

Thomas A Guilliam, Joseph Tp Yeeles

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. DNA polymerase α-primase can function as a translesion DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  17. Beyond the Lesion: Back to High Fidelity DNA Synthesis.Frontiers in molecular biosciences · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Thomas A GuilliamDivision of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0003-0065-2693
Joseph Tp YeelesDivision of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-2255-2119
MRC Laboratory of Molecular Biology · GB

Funding

Medical Research Council MC_UP_1201/12Wellcome TrustWellcome Trust 213596/Z/18/Z
6 · The paper itself

Abstract

The high-fidelity replicative DNA polymerases, Pol ε and Pol δ, are generally thought to be poorly equipped to replicate damaged DNA. Direct and complete replication of a damaged template therefore typically requires the activity of low-fidelity translesion synthesis (TLS) polymerases. Here we show that a yeast replisome, reconstituted with purified proteins, is inherently tolerant of the common oxidative lesion thymine glycol (Tg). Surprisingly, leading-strand Tg was bypassed efficiently in the presence and absence of the TLS machinery. Our data reveal that following helicase-polymerase uncoupling a switch from Pol ε, the canonical leading-strand replicase, to the lagging-strand replicase Pol δ, facilitates rapid, efficient and error-free lesion bypass at physiological nucleotide levels. This replicase switch mechanism also promotes bypass of the unrelated oxidative lesion, 8-oxoguanine. We propose that replicase switching may promote continued leading-strand synthesis whenever the replisome encounters leading-strand damage that is bypassed more efficiently by Pol δ than by Pol ε.

Indexed as

DNA DamageDNA ReplicationDNA-Directed DNA PolymeraseSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsThymineDNA-Directed DNA PolymeraseDNA replicaseSaccharomyces cerevisiae ProteinsThyminethymine glycolDNA damage toleranceDNA polymeraseDNA replicationreplisometranslesion synthesis

Identifiers

PMID33555053
PMCPMC7917549
OpenAlexW3126350730

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.