整合子3是单链DNA结合蛋白1的一个伙伴，参与DNA损伤反应。
Integrator3, a partner of single-stranded DNA-binding protein 1, participates in the DNA damage response.
作者信息
Zhang Feng, Wu Jiaxue, Yu Xiaochun
机构信息
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
出版信息
J Biol Chem. 2009 Oct 30;284(44):30408-15. doi: 10.1074/jbc.M109.039404. Epub 2009 Sep 15.
Abstract
Single-stranded DNA-binding protein 1 (SSB1) plays an important role in the DNA damage response and maintenance of genomic stability. Here, by using protein affinity purification, we have identified Integrator3 (INT3) as a novel partner of SSB1. INT3 forms a complex with SSB1 by constitutively interacting with SSB1 regardless of DNA damage. However, following DNA damage, along with SSB1, INT3 relocates to the DNA damage sites and regulates the accumulation of TopBP1 and BRCA1 there. Moreover, INT3 controls DNA damage-induced Chk1 activation and G(2)/M checkpoint activation. In addition, INT3 is involved in homologous recombination repair by regulating Rad51 foci formation following DNA damage. Taken together, these results demonstrate that INT3 plays a key role in the DNA damage response.
摘要
单链DNA结合蛋白1（SSB1）在DNA损伤应答和基因组稳定性维持中发挥重要作用。在此，我们通过蛋白质亲和纯化，鉴定出整合因子3（INT3）是SSB1的一个新伙伴。无论DNA是否损伤，INT3通过与SSB1持续相互作用而与SSB1形成复合物。然而，在DNA损伤后，INT3与SSB1一起重新定位到DNA损伤位点，并调节那里TopBP1和BRCA1的积累。此外，INT3控制DNA损伤诱导的Chk1激活和G(2)/M期检查点激活。另外，INT3通过在DNA损伤后调节Rad51灶形成参与同源重组修复。综上所述，这些结果表明INT3在DNA损伤应答中起关键作用。
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