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Cited by 389

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells

Open access
Garaycoechea, Juan I., Crossan, Gerry P., Langevin, Frédéric, Mulderrig, Lee, Louzada, Sandra, Yang, Fentang, Guilbaud, Guillaume, Park, Naomi, Roerink, Sophie, Nik-Zainal, Serena, Stratton, Michael R., Patel, Ketan J.·2018·Nature

Abstract

Haematopoietic stem cells renew blood. Accumulation of DNA damage in these cells promotes their decline, while misrepair of this damage initiates malignancies. Here we describe the features and mutational landscape of DNA damage caused by acetaldehyde, an endogenous and alcohol-derived metabolite. This damage results in DNA double-stranded breaks that, despite stimulating recombination repair, also cause chromosome rearrangements. We combined transplantation of single haematopoietic stem cells with whole-genome sequencing to show that this damage occurs in stem cells, leading to deletions and rearrangements that are indicative of microhomology-mediated end-joining repair. Moreover, deletion of p53 completely rescues the survival of aldehyde-stressed and mutated haematopoietic stem cells, but does not change the pattern or the intensity of genome instability within individual stem cells. These findings characterize the mutation of the stem-cell genome by an alcohol-derived and endogenous source of DNA damage. Furthermore, we identify how the choice of DNA-repair pathway and a stringent p53 response limit the transmission of aldehyde-induced mutations in stem cells.

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Metadata

Authors
Garaycoechea, J. I., Crossan, G. P., Langevin, F., Mulderrig, L., Louzada, S., Yang, F., Guilbaud, G., Park, N., Roerink, S., Nik-Zainal, S., Stratton, M. R., & Patel, K. J.
Venue
Nature
Published
2018-01
Volume
553
Issue
7687
Pages
171-177
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2781490247
Cited by
389
References
43
FWCI
14.60
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells. https://app.cochat.ai/papers/10.1038/nature25154
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Garaycoechea, J. I., Crossan, G. P., Langevin, F., Mulderrig, L., Louzada, S., Yang, F., Guilbaud, G., Park, N., Roerink, S., Nik-Zainal, S., Stratton, M. R., & Patel, K. J. (2018). Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells. Nature. https://doi.org/10.1038/nature25154

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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