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Identification and functional characterizations of N-Terminal a-N-Methylation and Phosphorylation of Serine 461 in human Poly(ADP-ribose) Polymerase 3
journal contribution
posted on 2023-06-08, 22:33 authored by Xiaoxia Dai, Stuart L Rulten, Changjun You, Keith CaldecottKeith Caldecott, Yinsheng WangPoly(ADP-ribose) polymerase 3 (PARP3) is a member of the PARP family enzymes which catalyze the ADP-ribosylation of proteins. PARP3 plays an important role in DNA damage repair and mitotic progression. In this study, we identified, using mass spectrometric techniques, two novel post-translational modification sites in PARP3, a-N-methylation and phosphorylation of serine 461 (S461). We found that the N-terminal a-amino group of PARP3 is heavily methylated in human cells, and N-terminal RCC1 methyltransferase (NRMT) is a key enzyme required for this methylation. We also observed that the phosphorylation level of S461 in PARP3 could be reduced in human cells upon treatment with flavopiridol, a cyclin-dependent kinase inhibitor. Moreover, we demonstrated that S461 phosphorylation, but not a-N-methylation of PARP3, may be involved in the cellular response toward DNA double-strand breaks. These findings provide novel insights into the post-translational regulation of PARP3.
Funding
Non-homologous End-Joining Protein Complexes and Genome Stability; G1305; CANCER RESEARCH UK; C6563/A16771
History
Publication status
- Published
Journal
Journal of proteome researchISSN
1535-3907Publisher
American Chemical SocietyExternal DOI
Issue
6Volume
14Page range
2575-2582Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- No
Peer reviewed?
- Yes