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Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that synthesise ADP-ribosylation (ADPr), a reversible modification of proteins that regulates many different cellular processes. Several mammalian PARPs are known to regulate the DNA damage response, but it is not clear which amino acids in proteins are the primary ADPr targets. Previously, we reported that ARH3 reverses the newly discovered type of ADPr (ADPr on serine residues; Ser-ADPr) and developed tools to analyse this modification (Fontana et al., 2017). Here, we show that Ser-ADPr represents the major fraction of ADPr synthesised after DNA damage in mammalian cells and that globally Ser-ADPr is dependent on HPF1, PARP1 and ARH3. In the absence of HPF1, glutamate/aspartate becomes the main target residues for ADPr. Furthermore, we describe a method for site-specific validation of serine ADP-ribosylated substrates in cells. Our study establishes serine as the primary form of ADPr in DNA damage signalling.
Pubmed ID: 29480802 RIS Download
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View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets PAR
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets mono ADP-ribose
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsThis polyclonal targets ADPRHL2
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets ADP-ribose
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsThis polyclonal targets ADPRHL2
View all literature mentionsThis monoclonal targets mono ADP-ribose
View all literature mentionsThis monoclonal targets ADP-ribose
View all literature mentionsThis polyclonal targets PAR
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets ADPRHL2
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis monoclonal targets mono ADP-ribose
View all literature mentionsThis monoclonal targets ADP-ribose
View all literature mentionsThis polyclonal targets PAR
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets ADPRHL2
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis monoclonal targets mono ADP-ribose
View all literature mentionsThis monoclonal targets ADP-ribose
View all literature mentionsThis polyclonal targets PAR
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets ADPRHL2
View all literature mentionsThis polyclonal targets Histone H3
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsThis monoclonal targets mono ADP-ribose
View all literature mentionsThis monoclonal targets ADP-ribose
View all literature mentionsThis polyclonal targets PAR
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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