Long-lived mammals contain more phosphorylation sites in the SIRT6 C-terminus that enhance PARP1 interaction and resistance to oxidative stress
analyses revealed that SIRT6 hyperphosphorylation enhances its interaction with PARP1. Mutating the T294 phosphorylation site in human fibroblasts led to decreased survival after oxidative stress in the phospho-null T294A and improved oxidative stress resistance in the phospho-mimetic T294E. Together, these results suggest SIRT6 C-terminal phosphorylation increases stress resistance through interaction with PARP1, and that this effect has been enhanced by evolution in long-lived species.
Authors
- Gregory Tombline
- Jonathan Gigas
- Kyle Swovick (ORCID: https://orcid.org/0000-0003-1161-7957)
- Kevin A. Welle (ORCID: https://orcid.org/0000-0003-2253-6896)
- Michael E. Meadow (ORCID: https://orcid.org/0000-0003-0766-7863)
- Philip M. Bellomio (ORCID: https://orcid.org/0009-0004-9613-5504)
- Julia Ablaeva (ORCID: https://orcid.org/0000-0002-0938-2629)
- Jennifer R. Hryhorenko (ORCID: https://orcid.org/0009-0009-5880-2667)
- Catherine Lan
- Eric Hillpot
- Jing Guo (ORCID: https://orcid.org/0000-0003-4440-6603)
- Sina Ghaemmaghami
- Andrei Seluanov
- Vera Gorbunova
- John C. Martinez
Institutions
- University of Rochester Medical Center (US)
- University of Rochester (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-24
- DOI
- https://doi.org/10.64898/2026.04.22.718469
- Primary Topic
- Sirtuins and Resveratrol in Medicine
- Type
- article
- Field-Weighted Citation Impact
- 0.00