SIRT1 stabilizes extrachromosomal gene amplification and contributes to repeat-induced gene silencing.

ABSTRACT: Sirtuin 1 (SIRT1) is a protein deacetylase that maintains genome stability by preventing the activation of latent replication origins. Amplified genes in cancer cells localize on either extrachromosomal double minutes (DMs) or the chromosomal homogeneously staining region. Previously, we found that a plasmid with a mammalian replication initiation region and a matrix attachment region spontaneously mimics gene amplification in cultured animal cells and efficiently generates DMs and/or an homogeneously staining region. Here, we addressed the possibility that SIRT1 might be involved in initiation region/matrix attachment region-mediated gene amplification using SIRT1-knockout human COLO 320DM cells. Consequently, we found that extrachromosomal amplification was infrequent in SIRT1-deficient

SUBMITTER: Taniguchi R 

PROVIDER: S-EPMC7949162 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature