SMC5/6-mediated plasmid silencing is directed by SIMC1-SLF2 and antagonized by the SV40 large T antigen.

ABSTRACT: SMC5/6 is unique among the Structural Maintenance of Chromosomes (SMC) complexes in its ability to repress transcription from extrachromosomal circular DNA (ecDNA), including viral genomes and plasmids. Previously, we showed that human SMC5/6 is regulated by two mutually exclusive subcomplexes-SIMC1-SLF2 and SLF1/2-the counterparts of yeast Nse5/6 (Oravcová et al., 2022). Notably, only SIMC1-SLF2 recruits SMC5/6 to SV40 large T antigen (LT) foci in PML nuclear bodies (PML NBs), suggesting that these regulatory subcomplexes direct distinct roles of SMC5/6 on chromosomal versus ecDNA. However, their roles in plasmid repression remain unclear. Here, we demonstrate that SMC5/6-mediated repression of plasmid transcription depends exclusively on SIMC1-SLF2, whereas SLF1/2 is dispensable. Reinfor

SUBMITTER: Oravcova M 

PROVIDER: S-EPMC12656486 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature