Concerns Regarding Site Inconsistency and Methodological Gaps in 'NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance' (Nature, 2024)

Academic fraud report · Geng Detector

Summary

This report, generated by an AI-assisted tool, flags concerns in the Nature 2024 article (DOI: 10.1038/s41586-024-07620-9) claiming that NBS1 lactylation at K388 drives DNA repair and chemotherapy resistance. The overall verdict is 'Questionable'. The most serious issue is an internal contradiction in the text: in the section describing LC–MS/MS identification and prime editing, the manuscript refers to 'K338' lactylation and a K338R substitution, yet immediately afterward names the cell line 'AGS-NBS1(K388R)'. The title, figures (Fig. 2g, 3a) and the rest of the paper consistently use K388. A secondary, lower-severity concern notes that the HGC27 cell line, used in key ECAR/lactate experiments, is missing from the Cell lines source list in Methods. Additional observations note a long review cycle (13 months) and flag that image-level forensics were not feasible from the text alone. No definitive misconduct is proven; findings require verification with raw mass spectra, Sanger traces, and original Western blots.

Verdict

🟡 Questionable — Text-level contradictions and methodological gaps raise serious concerns about data integrity and editorial care, but no conclusive evidence of image manipulation or data fabrication is established from the available source.

Key findings

Core site inconsistency (K388 vs K338): The mass spectrometry and prime-editing paragraphs explicitly name lysine 338, while the immediately following sentence and the rest of the paper use K388R/K388.
Missing cell line provenance: HGC27-P/-R cells are used in ECAR/lactate assays (Extended Data Fig. 8f and main text) but are absent from the Methods 'Cell lines' source list, unlike AGS, A549, HCT116, HeLa, MGC803, U2OS-265, and 293T.
Prolonged review timeline: Received 18 April 2023, accepted 29 May 2024 (~13 months), notable given the unusually large data volume (4D label-free lactyl-proteomics, CLMS, PDX, PDO, multiple clinical cohorts).
Image analysis not performed: The report explicitly states forensic analysis of Western blots and IPs was not possible due to lack of high-resolution original images.

Evidence highlights

K338 → K388 swap (p. 666): "LC–MS/MS revealed that K338 of NBS1 was lactylated (Fig. 2f). We used prime editing of the genome of AGS-P cells to replace NBS1 lysine 338 with arginine (Extended Data Fig. 5b). NBS1 protein could not be lactylated in AGS-NBS1(K388R) cells..." — two sentences later, the site label flips without explanation.
HGC27 omission: Methods enumerate ATCC/SIBCB sources for 293T, AGS, A549, HCT116, HeLa, MGC803, U2OS-265 but omit HGC27, which is central to lactate-production and ECAR comparisons in Extended Data Fig. 8f.
DOI: 10.1038/s41586-024-07620-9 (Nature Vol. 631, 18 July 2024).

Notes

The site inconsistency is the most damaging single issue: it affects the central mechanistic claim of the paper and could indicate a copy-paste error or an undeclared correction of an earlier, possibly fabricated, site assignment.
The cell-line source gap alone is minor, but combined with the site swap it suggests inadequate editorial checking.
Recommended follow-ups: request raw LC–MS/MS spectra for the identified lactylation site, full Sanger sequencing chromatograms of the prime-edited AGS-NBS1 line, uncut high-resolution Western blot images, and watch for any Erratum from the authors.
All conclusions are provisional pending review of original source data; this report does not constitute a formal finding of misconduct.