SIRT1 Prevents R-Loops during Chronological Aging by Modulating DNA Replication at rDNA Loci.

ABSTRACT: In metazoans, the largest sirtuin, SIRT1, is a nuclear protein implicated in epigenetic modifications, circadian signaling, DNA recombination, replication, and repair. Our previous studies have demonstrated that SIRT1 binds replication origins and inhibits replication initiation from a group of potential initiation sites (dormant origins). We studied the effects of aging and SIRT1 activity on replication origin usage and the incidence of transcription-replication collisions (creating R-loop structures) in adult human cells obtained at different time points during chronological aging and in cancer cells. In primary, untransformed cells, SIRT1 activity declined and the prevalence of R-loops rose with chronological aging. Both the reduction in SIRT1 activity and the increased abundance of R-l

SUBMITTER: Thakur BL 

PROVIDER: S-EPMC10669956 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature