Crystal structure and mutagenesis of a nucleic acid-binding BRCT domain in human PARP4.

ABSTRACT: PARP4 is an ADP-ribosyltransferase typically associated with the cytoplasmic vault organelle. PARP4 has a distinct domain composition relative to other PARP enzymes; however, the N-terminal region of PARP4 is homologous to a collection of domains found in PARP1, a regulator of multiple nuclear processes including the cellular response to DNA damage. The N-terminal region of PARP4 interacts in vitro with nucleic acid, in particular a noncoding RNA associated with vault particles, and a BRCT domain is implicated in this interaction. Here, we report the X-ray structure of the BRCT domain of PARP4 and structure-based mutagenesis that interrogates the nucleic acid-binding activity using vault RNA. The isolated BRCT domain is capable of mediating interaction with vault RNA, and we identified fou

SUBMITTER: Frigon L 

PROVIDER: S-EPMC12212138 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature