Evidence map›Paper›PMID 36085347›Full record

ArticleNature communications2022

Lagging strand gap suppression connects BRCA-mediated fork protection to nucleosome assembly through PCNA-dependent CAF-1 recycling.

Tanay Thakar, Ashna Dhoonmoon, Joshua Straka, Emily M Schleicher, Claudia M Nicolae, George-Lucian Moldovan

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

28 citing papers in PubMed, 31 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

6 authors at 1 institution in 1 country.

Tanay ThakarDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.ORCID 0000-0001-5261-458X
Ashna DhoonmoonDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
Joshua StrakaDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
Emily M SchleicherDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.
Claudia M NicolaeDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.ORCID 0000-0003-4933-5496
George-Lucian MoldovanDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. glm29@psu.edu.ORCID 0000-0003-3825-149X
Pennsylvania State University · US

Funding

The Role of Mono-ADP-Ribosylation by PARP14 in RadioresistanceR01ES026184 · NIEHS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI George Lucian Moldovan · 2016 to 2026
$3.6M
The role of DNA damage tolerance pathways in human cellsR01GM134681 · NIGMS · UNIVERSITY OF VIRGINIA · PI George Lucian Moldovan, Claudia M Nicolae · 2019 to 2026
$3.0M
The role of PARP10 in alleviating replication stress and promoting cellular proliferation and tumorigenesisR01CA244417 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI NICOLAE, CLAUDIA M · 2021 to 2025
$1.8M
NCI NIH HHS R01 CA244417NIEHS NIH HHS R01 ES026184NIGMS NIH HHS R01 GM134681
6 · The paper itself

Abstract

The inability to protect stalled replication forks from nucleolytic degradation drives genome instability and underlies chemosensitivity in BRCA-deficient tumors. An emerging hallmark of BRCA-deficiency is the inability to suppress replication-associated single-stranded DNA (ssDNA) gaps. Here, we report that lagging strand ssDNA gaps interfere with the ASF1-CAF-1 nucleosome assembly pathway, and drive fork degradation in BRCA-deficient cells. We show that CAF-1 function at replication forks is lost in BRCA-deficient cells, due to defects in its recycling during replication stress. This CAF-1 recycling defect is caused by lagging strand gaps which preclude PCNA unloading, causing sequestration of PCNA-CAF-1 complexes on chromatin. Importantly, correcting PCNA unloading defects in BRCA-deficient cells restores CAF-1-dependent fork stability. We further show that the activation of a HIRA-dependent compensatory histone deposition pathway restores fork stability to BRCA-deficient cells. We thus define lagging strand gap suppression and nucleosome assembly as critical enablers of BRCA-mediated fork stability.

Indexed as

Chromatin Assembly and DisassemblyNucleosomesChromatin Assembly Factor-1DNA, Single-StrandedProliferating Cell Nuclear AntigenRecyclingChromatin Assembly Factor-1DNA, Single-StrandedNucleosomesProliferating Cell Nuclear Antigen

Identifiers

PMID36085347
PMCPMC9463168
OpenAlexW4295027168

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.