Evidence map›Paper›PMID 41005313›Full record

ArticleStem cell reports2025

Probing DNA damage in Rett syndrome neurons uncovers a role for MECP2 regulation of PARP1.

A Morales, E Korsakova, N Mansooralavi, A Ravikumar, G Rivas, P Soliman, L Rodriguez, T McDaniel, A Lund, B Cooper and 2 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

A MoralesMolecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
E KorsakovaMolecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Broad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
N MansooralaviMolecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Broad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA.
A RavikumarDepartment of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
G RivasDepartment of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
P SolimanDepartment of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Broad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
L RodriguezDepartment of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Broad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
T McDanielDepartment of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
A LundDepartment of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
B CooperDepartment of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
A BhaduriBroad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Department of Biological Chemistry, DGSOM, UCLA, Los Angeles, CA 90095, USA.
W E LowryMolecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Division of Dermatology, DGSOM, UCLA, Los Angeles, CA 90095, USA; Broad Center for Regenerative Medicine, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA. Electronic address: blowry@ucla.edu.

Funding

Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
NINDS NIH HHS T32 NS048004
6 · The paper itself

Abstract

Methyl-CpG-binding protein 2 (MECP2)/Rett syndrome is characterized by a postnatal loss of neurophysiological function and regression of childhood development. While Rett neurons have been described as showing elevated senescence and P53 activity, here we show that molecular and physiological dysfunction in neurons lacking MECP2 is triggered by elevated DNA damage. Using human induced pluripotent stem cell (hiPSC)-derived isogenic lines, we find that MECP2 directly interacts with members of the DNA repair machinery, including PARP1. Here, we present evidence that MECP2 also regulates PARP1 activity, and restoration of PARP1 activity in MECP2-null neurons can reverse DNA damage, senescence, dendritic branching defects, and metabolic dysfunction. These data from a human disease-in-a-dish model system support the notion that dysfunction in Rett syndrome neurons could be caused by changes in PARP activity.

Indexed as

DNA DamageMethyl-CpG-Binding Protein 2NeuronsPoly (ADP-Ribose) Polymerase-1Rett SyndromeAnimalsCellular SenescenceDNA RepairHumansInduced Pluripotent Stem CellsProtein BindingMECP2 protein, humanMethyl-CpG-Binding Protein 2PARP1 protein, humanPoly (ADP-Ribose) Polymerase-1CDKL5DNA repairhuman neuronsintellectual disabilityMECP2PARP1Rett syndromesenescence

Identifiers

PMID41005313
PMCPMC12790717

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.