HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation.

ABSTRACT: The anti-cancer drug target poly(ADP-ribose) polymerase 1 (PARP1) and its close homologue, PARP2, are early responders to DNA damage in human cells^1,2. After binding to genomic lesions, these enzymes use NAD⁺ to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors^3,4. These post-translational modifications are predominantly serine-linked and require the accessory factor HPF1, which is specific for the DNA damage response and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues^5-10. Here we report a co-structure of HPF1 bound to the catalytic domain of PARP2 that, in combination with NMR

SUBMITTER: Suskiewicz MJ 

PROVIDER: S-EPMC7104379 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature