Evidence map›Paper›PMID 19440204›Full record

ArticleThe EMBO journal2009

Active site electrostatics protect genome integrity by blocking abortive hydrolysis during DNA recombination.

Chien-Hui Ma, Paul A Rowley, Anna Macieszak, Piotr Guga, Makkuni Jayaram

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

10 citing papers in PubMed, 21 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

5 authors at 3 institutions in 2 countries.

Chien-Hui MaSection of Molecular Genetics and Microbiology, University of Texas at Austin, TX 78712, USA.
Paul A Rowley
Anna Macieszak
Piotr Guga
Makkuni Jayaram
The University of Texas at Austin · USCentrum Badań Molekularnych i Makromolekularnych Polskiej Akademii Nauk · PLPolish Academy of Sciences · PL

Funding

SITE SPECIFIC RECOMBINATION IN THE YEAST PLASMIDR01GM035654 · NIGMS · UNIVERSITY OF TEXAS AUSTIN · PI JAYARAM, MAKKUNI · 1986 to 2009
$4.0M
NIGMS NIH HHS GM035654NIGMS NIH HHS R01 GM035654
6 · The paper itself

Abstract

Water, acting as a rogue nucleophile, can disrupt transesterification steps of important phosphoryl transfer reactions in DNA and RNA. We have unveiled this risk, and identified safeguards instituted against it, during strand cleavage and joining by the tyrosine site-specific recombinase Flp. Strand joining is threatened by a latent Flp endonuclease activity (type I) towards the 3'-phosphotyrosyl intermediate resulting from strand cleavage. This risk is not alleviated by phosphate electrostatics; neutralizing the negative charge on the scissile phosphate through methylphosphonate (MeP) substitution does not stimulate type I endonuclease. Rather, protection derives from the architecture of the recombination synapse and conformational dynamics within it. Strand cleavage is protected against water by active site electrostatics. Replacement of the catalytic Arg-308 of Flp by alanine, along with MeP substitution, elicits a second Flp endonuclease activity (type II) that directly targets the scissile phosphodiester bond in DNA. MeP substitution, combined with appropriate active site mutations, will be useful in revealing anti-hydrolytic mechanisms engendered by systems that mediate DNA relaxation, DNA transposition, site-specific recombination, telomere resolution, RNA splicing and retrohoming of mobile introns.

Indexed as

Static ElectricityAmino AcidsAmino Acid SubstitutionCatalytic DomainDNADNA NucleotidyltransferasesEndonucleasesEsterificationGenomeHydrolysisKineticsModels, BiologicalOrganophosphorus CompoundsRecombination, GeneticStereoisomerismSubstrate SpecificityAmino AcidsDNADNA NucleotidyltransferasesEndonucleasesFLP recombinasemethylphosphonic acidOrganophosphorus Compounds

Identifiers

PMID19440204
PMCPMC2699359
OpenAlexW2134965440

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.