期刊
FEBS JOURNAL
卷 288, 期 7, 页码 2131-2142出版社
WILEY
DOI: 10.1111/febs.15518
关键词
ADP-ribosylation; DNA repair; enzymatic catalysis; HPF1; PARP; PARP1; PARP9; poly(ADP-ribosylation); post-translational modification; specificity
资金
- EMBO Long-term Fellowship [879-2017]
- Italian Foundation for Cancer Research (FIRC) [14895]
- Regione Campania under POR Campania FESR 2014/2020 (SATIN)
- Wellcome Trust [101794, 210634]
- Biotechnology and Biological Sciences Research Council [BB/R007195/1]
- Cancer Research United Kingdom [C35050/A22284]
- BBSRC [BB/R007195/1] Funding Source: UKRI
Despite years of research on ADP-ribosyltransferases from the PARP family, their substrate specificity has remained unclear. Recent breakthroughs include identifying protein serine residues, cysteine, and tyrosine as potential targets of specific PARPs. These findings shed new light on PARP-mediated catalysis and caution to expect the unexpected with potential substrates.
Despite decades of research on ADP-ribosyltransferases (ARTs) from the poly(ADP-ribose) polymerase (PARP) family, one key aspect of these enzymes - their substrate specificity - has remained unclear. Here, we briefly discuss the history of this area and, more extensively, the recent breakthroughs, including the identification of protein serine residues as a major substrate of PARP1 and PARP2 in human cells and of cysteine and tyrosine as potential targets of specific PARPs. On the molecular level, the modification of serine residues requires a composite active site formed by PARP1 or PARP2 together with a specificity-determining factor, HPF1; this represents a new paradigm not only for PARPs but generally for post-translational modification (PTM) catalysis. Additionally, we discuss the identification of DNA as a substrate of PARP1, PARP2 and PARP3, and some bacterial ARTs and the discovery of noncanonical RNA capping by several PARP family members. Together, these recent findings shed new light on PARP-mediated catalysis and caution to 'expect the unexpected' when it comes to further potential substrates.
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