Evidence map›Paper›PMID 36053906›Full record

ArticleMolecular microbiology2022

Multiple mechanisms for overcoming lethal over-initiation of DNA replication.

Mary E Anderson, Janet L Smith, Alan D Grossman

Open access · hybridAbstract read
In one paragraph

Article in Molecular microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 29% 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

8 citing papers in PubMed, 10 citations in OpenAlex.

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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

3 authors at 1 institution in 1 country.

Mary E AndersonDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0002-6930-3830
Janet L SmithDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0001-7983-5534
Alan D GrossmanDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0002-8235-7227
Massachusetts Institute of Technology · US

Funding

Cell Cycle and Sporulation in Bacillis SubtillisR37GM041934 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GROSSMAN, ALAN D · 2009 to 2017
$4.8M
Mechanisms and regulation of replication, the cell cycle, gene expression, and horizontal gene transfer in prokaryotes, focusing on Bacillus subtilisR35GM122538 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GROSSMAN, ALAN D · 2017 to 2021
$3.2M
INITITATION OF SPORULATION IN BACILLUS SUBTILISR01GM041934 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GROSSMAN, ALAN D · 1989 to 2007
$2.6M
NIGMS NIH HHS R01 GM041934NIGMS NIH HHS R35 GM122538NIGMS NIH HHS R37 GM041934
6 · The paper itself

Abstract

DNA replication is highly regulated and primarily controlled at the step of initiation. In bacteria, the replication initiator DnaA and the origin of replication oriC are the primary targets of regulation. Perturbations that increase or decrease replication initiation can cause a decrease in cell fitness. We found that multiple mechanisms, including an increase in replication elongation and a decrease in replication initiation, can compensate for lethal over-initiation. We found that in Bacillus subtilis, under conditions of rapid growth, loss of yabA, a negative regulator of replication initiation, caused a synthetic lethal phenotype when combined with the dnaA1 mutation that also causes replication over-initiation. We isolated several classes of suppressors that restored viability to dnaA1 ∆yabA double mutants. Some suppressors (relA, nrdR) stimulated replication elongation. Others (dnaC, cshA) caused a decrease in replication initiation. One class of suppressors decreased replication initiation in the dnaA1 ∆yabA mutant by causing a decrease in the amount of the replicative helicase, DnaC. We found that decreased levels of helicase in otherwise wild-type cells were sufficient to decrease replication initiation during rapid growth, indicating that the replicative helicase is limiting for replication initiation. Our results highlight the multiple mechanisms cells use to regulate DNA replication.

Indexed as

Bacterial ProteinsDNA-Binding ProteinsBacillus subtilisDNA HelicasesDNA ReplicationReplication OriginBacterial ProteinsDNA-Binding ProteinsDNA HelicasesBacillus subtilisDNA helicaseDNA replicationreplication elongationreplication initiation

Identifiers

PMID36053906
PMCPMC9825946
OpenAlexW4293368072

What OpenQuestion holds

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LicenceCC BY-NC
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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 OpenQuestion graph.