Autoantibodies reacting with poly(ADP-ribose) and with a zinc-finger functional domain of poly(ADP-ribose) polymerase involved in the recognition of damaged DNA.
Poly(ADP-Ribose) polymerase (PARP) is a chromatin-associated enzyme that specifically binds to DNA strand breaks in a zinc-dependent manner. We describe here the presence of IgG antibodies reacting with recombinant human PARP in the serum of patients with systemic lupus erythematosus (SLE) and primary and secondary Sjögren's syndrome (pSS and sSS). The reactivity of patients' sera was further studied in ELISA with a synthetic peptide of 44 residues corresponding to the second zinc finger (F2) present in the DNA-binding domain of PARP and which was shown to effectively bind 65Zn. Thirty-five percent of SLE sera (n = 97), 42% of pSS sera (n = 67), and 56% of sSS sera (n = 16) were found to contain raised levels of IgG antibodies reacting with peptide F2 which corresponds to the domain in PARP that is directly involved in the specific recognition of single and double strand breaks in DNA. Antibodies reacting with the whole enzyme and/or peptide F2 occurred independently from antibodies reacting with poly(ADP-ribose) which is rapidly synthesized in vivo by PARP from NAD and then degraded in response to DNA strand breaks.
Muller
S
S
UPR 9021, CNRS, Strasbourg, France.
Briand
J P
JP
Barakat
S
S
Lagueux
J
J
Poirier
G G
GG
De Murcia
G
G
Isenberg
D A
DA
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007106:Immune Sera / Q000737:chemistry; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000276:immunology*; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000276:immunology; D016335:Zinc Fingers / Q000276:immunology*
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D007106:Immune Sera; D010446:Peptide Fragments; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases