Control of replication and gene expression by ADP-ribosylation of DNA in Mycobacterium tuberculosis.

ABSTRACT: Mycobacterium tuberculosis maintains long-term infections characterised by the need to regulate growth and adapt to contrasting in vivo environments. Here we show that M. tuberculosis complex bacteria utilise reversible ADP-ribosylation of single-stranded DNA as a mechanism to coordinate stationary phase growth with transcriptional adaptation. The DNA modification is controlled by DarT, an ADP-ribosyltransferase, which adds ADP-ribose to thymidine, and DarG, which enzymatically removes this base modification. Using darG-knockdown M. bovis BCG, we map the first DNA ADP-ribosylome from any organism. We show that inhibition of replication by DarT is reversible and accompanied by extensive ADP-ribosylation at the origin of replication (OriC). In addition, we observe ADP-ribosylation across the

SUBMITTER: Butler RE 

PROVIDER: S-EPMC12170906 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature