Obesity increases genomic instability at DNA repeat-mediated endogenous mutation hotspots

Pallavi Kompella, Guliang Wang, Russell E. Durrett, Yanhao Lai, Celeste Marin, Yuan Liu, Samy L. Habib, John DiGiovanni and Karen M. Vasquez ()
Additional contact information
Pallavi Kompella: Dell Pediatric Research Institute
Guliang Wang: Dell Pediatric Research Institute
Russell E. Durrett: The University of Texas at Austin
Yanhao Lai: Florida International University
Celeste Marin: Florida International University
Yuan Liu: Florida International University
Samy L. Habib: South Texas Veterans Health Care System
John DiGiovanni: Dell Pediatric Research Institute
Karen M. Vasquez: Dell Pediatric Research Institute

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Obesity is associated with increased cancer risk, yet the underlying mechanisms remain elusive. Obesity-associated cancers involve disruptions in metabolic and cellular pathways, which can lead to genomic instability. Repetitive DNA sequences capable of adopting alternative DNA structures (e.g., H-DNA) stimulate mutations and are enriched at mutation hotspots in human cancer genomes. However, it is not known if obesity impacts DNA repeat-mediated endogenous mutation hotspots. We address this gap by measuring mutation frequencies in obese and normal-weight transgenic reporter mice carrying either a control human B-DNA- or an H-DNA-forming sequence (from a translocation hotspot in c-MYC in Burkitt lymphoma). Here, we discover that H-DNA-induced DNA damage and mutations are elevated in a tissue-specific manner, and DNA repair efficiency is reduced in obese mice compared to those on the control diet. These findings elucidate the impact of obesity on cancer-associated endogenous mutation hotspots, providing mechanistic insight into the link between obesity and cancer.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-50006-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50006-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-50006-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().