Evidence map›Paper›PMID 36269050›Full record

ArticleeLife2022

KAT2-mediated acetylation switches the mode of PALB2 chromatin association to safeguard genome integrity.

Marjorie Fournier, Amélie Rodrigue, Larissa Milano, Jean-Yves Bleuyard, Anthony M Couturier, Jacob Wall, Jessica Ellins, Svenja Hester, Stephen J Smerdon, László Tora and 2 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. 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
0.6field-weighted citation impact, top 35% 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, 8 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

12 authors at 4 institutions in 5 countries.

Marjorie FournierSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-4075-8719
Amélie RodrigueCHU de Québec Research Center, Oncology Division; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Québec, Canada.ORCID 0000-0001-9883-7084
Larissa MilanoCHU de Québec Research Center, Oncology Division; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Québec, Canada.
Jean-Yves BleuyardSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-6727-5362
Anthony M CouturierSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-1512-9558
Jacob WallSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Jessica EllinsDepartment of Biochemistry, University of Oxford, Oxford, United Kingdom.
Svenja HesterSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Stephen J SmerdonThe Francis Crick Institute, London, United Kingdom.ORCID 0000-0001-5688-8465
László ToraInstitut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.ORCID 0000-0001-7398-2250
Jean-Yves MassonCHU de Québec Research Center, Oncology Division; Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University Cancer Research Center, Québec, Canada.ORCID 0000-0002-4403-7169
Fumiko EsashiSir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.ORCID 0000-0003-0902-2364
University of Oxford · GBCancer Research Center · USCentre National de la Recherche Scientifique · FRThe Francis Crick Institute · GB

Funding

Cancer Research UKMedical Research Council MR/W017601Medical Research Council MR/W017601/1Wellcome Trust 101009/Z/13/ZWellcome Trust FC001156
6 · The paper itself

Abstract

The tumour suppressor PALB2 stimulates RAD51-mediated homologous recombination (HR) repair of DNA damage, whilst its steady-state association with active genes protects these loci from replication stress. Here, we report that the lysine acetyltransferases 2A and 2B (KAT2A/2B, also called GCN5/PCAF), two well-known transcriptional regulators, acetylate a cluster of seven lysine residues (7K-patch) within the PALB2 chromatin association motif (ChAM) and, in this way, regulate context-dependent PALB2 binding to chromatin. In unperturbed cells, the 7K-patch is targeted for KAT2A/2B-mediated acetylation, which in turn enhances the direct association of PALB2 with nucleosomes. Importantly, DNA damage triggers a rapid deacetylation of ChAM and increases the overall mobility of PALB2. Distinct missense mutations of the 7K-patch render the mode of PALB2 chromatin binding, making it either unstably chromatin-bound (7Q) or randomly bound with a reduced capacity for mobilisation (7R). Significantly, both of these mutations confer a deficiency in RAD51 foci formation and increase DNA damage in S phase, leading to the reduction of overall cell survival. Thus, our study reveals that acetylation of the ChAM 7K-patch acts as a molecular switch to enable dynamic PALB2 shuttling for HR repair while protecting active genes during DNA replication.

Indexed as

ChromatinTumor Suppressor ProteinsAcetylationDNA DamageDNA RepairNucleosomesChromatinNucleosomesTumor Suppressor ProteinsacetylationchromatinchromosomesDNA repairgene expressiongenome stabilityhumanKAT2PALB2

Identifiers

PMID36269050
PMCPMC9671498
OpenAlexW4307036039

What OpenQuestion 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 OpenQuestion graph.