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与聚(ADP - 核糖)以及参与受损DNA识别的聚(ADP - 核糖)聚合酶的锌指功能结构域发生反应的自身抗体。

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.

作者信息

Muller S, Briand J P, Barakat S, Lagueux J, Poirier G G, De Murcia G, Isenberg D A

机构信息

UPR 9021, CNRS, Strasbourg, France.

出版信息

Clin Immunol Immunopathol. 1994 Nov;73(2):187-96. doi: 10.1006/clin.1994.1187.

DOI:10.1006/clin.1994.1187
PMID:7923925
Abstract

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.

摘要

聚(ADP - 核糖)聚合酶(PARP)是一种与染色质相关的酶,它以锌依赖的方式特异性结合DNA链断裂处。我们在此描述了系统性红斑狼疮(SLE)、原发性和继发性干燥综合征(pSS和sSS)患者血清中存在与重组人PARP发生反应的IgG抗体。用与PARP DNA结合域中存在的第二个锌指(F2)对应的44个残基的合成肽,通过酶联免疫吸附测定(ELISA)进一步研究患者血清的反应性,该合成肽已显示能有效结合65Zn。发现35%的SLE血清(n = 97)、42%的pSS血清(n = 67)和56%的sSS血清(n = 16)含有与肽F2发生反应的IgG抗体水平升高,肽F2对应于PARP中直接参与DNA单链和双链断裂特异性识别的结构域。与整个酶和/或肽F2发生反应的抗体独立于与聚(ADP - 核糖)发生反应的抗体,聚(ADP - 核糖)是PARP在体内由NAD快速合成,然后响应DNA链断裂而降解的。

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