Physical and Functional Interaction between DNA Ligase IIIα and Poly(ADP-Ribose) Polymerase 1 in DNA Single-Strand Break Repair

John B. Leppard; Zhiwan Dong; Zachary B. Mackey; Alan E. Tomkinson

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Physical and Functional Interaction between DNA Ligase IIIα and Poly(ADP-Ribose) Polymerase 1 in DNA Single-Strand Break Repair

机译：DNA连接酶IIIα与聚（ADP-核糖）聚合酶1在DNA单链断裂修复中的物理和功能相互作用

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The repair of DNA single-strand breaks in mammalian cells is mediated by poly(ADP-ribose) polymerase 1 (PARP-1), DNA ligase IIIα, and XRCC1. Since these proteins are not found in lower eukaryotes, this DNA repair pathway plays a unique role in maintaining genome stability in more complex organisms. XRCC1 not only forms a stable complex with DNA ligase IIIα but also interacts with several other DNA repair factors. Here we have used affinity chromatography to identify proteins that associate with DNA ligase III. PARP-1 binds directly to an N-terminal region of DNA ligase III immediately adjacent to its zinc finger. In further studies, we have shown that DNA ligase III also binds directly to poly(ADP-ribose) and preferentially associates with poly(ADP-ribosyl)ated PARP-1 in vitro and in vivo. Our biochemical studies have revealed that the zinc finger of DNA ligase III increases DNA joining in the presence of either poly(ADP-ribosyl)ated PARP-1 or poly(ADP-ribose). This provides a mechanism for the recruitment of the DNA ligase IIIα-XRCC1 complex to in vivo DNA single-strand breaks and suggests that the zinc finger of DNA ligase III enables this complex and associated repair factors to locate the strand break in the presence of the negatively charged poly(ADP-ribose) polymer.

机译：哺乳动物细胞中DNA单链断裂的修复是由聚（ADP-核糖）聚合酶1（PARP-1），DNA连接酶IIIα和XRCC1介导的。由于在低等真核生物中未发现这些蛋白质，因此这种DNA修复途径在维持更为复杂的生物体的基因组稳定性中起着独特的作用。 XRCC1不仅与DNA连接酶IIIα形成稳定的复合物，而且还与其他几种DNA修复因子相互作用。在这里，我们已经使用亲和层析来鉴定与DNA连接酶III相关的蛋白质。 PARP-1直接与紧邻其锌指的DNA连接酶III的N端区域直接结合。在进一步的研究中，我们显示了DNA连接酶III在体外和体内也直接与聚（ADP-核糖）化的PARP-1结合，并优先与聚（ADP-核糖基）化的PARP-1结合。我们的生化研究表明，在存在聚（ADP-核糖基）化的PARP-1或聚（ADP-核糖）的情况下，DNA连接酶III的锌指会增加DNA连接。这提供了将DNA连接酶IIIα-XRCC1复合物募集到体内DNA单链断裂的机制，并且表明DNA连接酶III的锌指使这种复合物和相关的修复因子能够在存在DNA的情况下定位链断裂。带负电荷的聚（ADP-核糖）聚合物。

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《Molecular and Cellular Biology》 |2003年第16期|共9页
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John B. Leppard; Zhiwan Dong; Zachary B. Mackey; Alan E. Tomkinson;
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中图分类细胞生物学;
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1. XRCC1 polypeptide interacts with DNA polymerase p and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro [J] . Keith W. Caldecott, Said Aoufouchi, Penny Johnson, Nucleic Acids Research . 1996,第22期

机译：XRCC1多肽与DNA聚合酶p以及可能的聚（ADP-核糖）聚合酶相互作用，而DNA连接酶III是体外的新型分子“缺口传感器”
2. XRCC1 Polypeptide Interacts with DNA Polymerase β and Possibly Poly (ADP-Ribose) Polymerase, and DNA Ligase III Is a Novel Molecular ‘Nick-Sensor' In Vitro [J] . Keith W. Caldecott, Penny Johnson, Said Aoufouchi, Nucleic acids research . 1996,第22期

机译：XRCC1多肽与DNA聚合酶β和可能的聚（ADP-核糖）聚合酶相互作用，而DNA连接酶III是一种新型的分子“尼克传感器”体外
3. Down-regulation of DNA repair synthesis at DNA single-strand interruptions in poly(ADP-ribose) polymerase-1 deficient murine cell extracts. [J] . Sanderson RJ, Lindahl T DNA repair . 2002,第7期

机译：在缺乏聚（ADP-核糖）聚合酶-1的鼠细胞提取物中，在DNA单链中断时DNA修复合成的下调。
4. Towards an understanding of protein-protein interaction network hierarchies. Analysis of DnaN (β)-binding peptide motifs in members of protein families interacting with the eubacterial processivity clamp, the β subunit of DNA Polymerase III [C] . Brian P. Dalrymple, Gene Wijffels, Kritaya Kongsuwan, Asia-Pacific Bioinformatics Conference(APBC 2003); 200302; Adelaide(AU) . 2003

机译：对蛋白质-蛋白质相互作用网络层次结构的理解。蛋白质家族成员与DNA聚合酶III的优生过程性钳位相互作用的DnaN（β）结合肽基序分析
5. An unexpected role for the DNA-repair protein poly (adp-ribose) polymerase I in the induction and maintenance of a pluripotent stem cell phenotype. [D] . Williams, Ambrose Jon. 2011

机译：DNA修复蛋白聚（核糖）聚合酶I在多能干细胞表型的诱导和维持中出乎意料的作用。
6. Physical and Functional Interaction between DNA Ligase IIIα and Poly(ADP-Ribose) Polymerase 1 in DNA Single-Strand Break Repair [O] . John B. Leppard, Zhiwan Dong, Zachary B. Mackey, 2003

机译：DNA连接酶IIIα与聚（ADP-核糖）聚合酶1在DNA单链断裂修复中的物理和功能相互作用
7. Physical and Functional Interaction between DNA Ligase IIIα and Poly(ADP-Ribose) Polymerase 1 in DNA Single-Strand Break Repair [O] . Leppard, John B., Dong, Zhiwan, Mackey, Zachary B., 2003

机译：DNA连接酶IIIα与聚（ADP-核糖）聚合酶1在DNA单链断裂修复中的物理和功能相互作用
8. Poly (ADP-Ribose) Polymerase (PARP) is Essential for Sulfur Mustard- Induced DNA Damage Repair, But Has No Role in DNA Ligase Activation [R] . Bhat, K. R. , Benton, B. J. , Ray, R. 2006

机译：聚（aDp-核糖）聚合酶（paRp）是硫芥子诱导的DNa损伤修复的必要条件，但在DNa连接酶激活中没有作用

Physical and Functional Interaction between DNA Ligase IIIα and Poly(ADP-Ribose) Polymerase 1 in DNA Single-Strand Break Repair

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