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Record W4291222654 · doi:10.1038/s41467-022-31820-4

XPC–PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair

2022· article· en· W4291222654 on OpenAlexafffund
Charlotte Blessing, Katja Apelt, Diana van den Heuvel, Claudia Gonzalez-Leal, Magdalena B. Rother, Melanie van der Woude, Román González‐Prieto, Adi Yifrach, Avital Parnas, Rashmi G. Shah, Tia Tyrsett Kuo, Daphne E.C. Boer, Jin Cai, Angela Kragten, Hyun-Suk Kim, Orlando D. Schärer, Alfred C.O. Vertegaal, Girish M. Shah, Sheera Adar, Hannes Lans, Haico van Attikum, Andreas G. Ladurner, Martijn S. Luijsterburg

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA Repair Mechanisms
Canadian institutionsUniversité Laval
FundersNational Cancer InstituteNational Institutes of HealthOncode InstituteNatural Sciences and Engineering Research Council of CanadaLeids Universitair Medisch CentrumKWF KankerbestrijdingDeutsche ForschungsgemeinschaftUniversité LavalIsrael Cancer AssociationNederlandse Organisatie voor Wetenschappelijk OnderzoekIsrael Cancer Research Fund
KeywordsChromatinDNA damageDNACell biologyPolymeraseDNA repairPARP1BiologyPoly ADP ribose polymeraseNucleotide excision repairChromatin remodelingChemistryGenetics

Abstract

fetched live from OpenAlex

Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.002

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.288
Teacher spread0.271 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations23
Published2022
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicDNA Repair MechanismsFrench-language works237,207