PARP1-HPF1 structure and dynamics on nicked DNA suggest a mechanism for acute and localized ADP-ribosylation - PubMed
4 days ago
- #PARP1
- #ADP-ribosylation
- #DNA damage
- PARP1 detects DNA strand breaks and synthesizes poly(ADP-ribose) modifications to signal DNA damage.
- HPF1 interacts with activated PARP1 to control modification site selection.
- Cryo-EM reveals the structure of full-length PARP1 engaging a DNA single-strand break with HPF1 and Timeless.
- PARP1 remains dynamic on DNA breaks, with the catalytic region showing high mobility.
- The organization of PARP1 domains on DNA releases a constitutively active catalytic region to modify surrounding molecules.
- The study provides insights into the mechanism of DNA break detection and catalytic activation by PARP1.