Histone PARylation factor 1 (HPF1, previously known as C4orf27) is a key regulator of ADP-ribosylation (ADPr) signaling in response to DNA damage. It forms a complex with PARP-1 (poly(ADP-ribose) polymerase 1), creating a composite active site. HPF1 is essential for Ser-ADPr (ADPr on serine residues), which represents the major fraction of ADPr synthesised after DNA damage. This protein is organised into two tightly-associated domains connected via an elaborate linker, showing an alpha-beta structure [1-4]. [1]. 27067600. HPF1/C4orf27 Is a PARP-1-Interacting Protein that Regulates PARP-1 ADP-Ribosylation Activity. Gibbs-Seymour I, Fontana P, Rack JGM, Ahel I;. Mol Cell. 2016;62:432-442. [2]. 28190768. Serine ADP-Ribosylation Depends on HPF1. Bonfiglio JJ, Fontana P, Zhang Q, Colby T, Gibbs-Seymour I, Atanassov I, Bartlett E, Zaja R, Ahel I, Matic I;. Mol Cell. 2017;65:932-940. [3]. 33589610. HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones. Sun FH, Zhao P, Zhang N, Kong LL, Wong CCL, Yun CH;. Nat Commun. 2021;12:1028. [4]. 32028527. HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation. Suskiewicz MJ, Zobel F, Ogden TEH, Fontana P, Ariza A, Yang JC, Zhu K, Bracken L, Hawthorne WJ, Ahel D, Neuhaus D, Ahel I;. Nature. 2020;579:598-602. (from Pfam)
GO Terms:- Biological Process:
- DNA damage response (GO:0006974)
- Biological Process:
- regulation of protein ADP-ribosylation (GO:0010835)
- Molecular Function:
- histone binding (GO:0042393)
- Date:
- 2024-10-16