Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, 5560 MSRBII, Ann Arbor, MI 48109, USA.
J Cell Sci. 2013 Nov 1;126(Pt 21):4850-5. doi: 10.1242/jcs.132514. Epub 2013 Aug 28.
Human single-stranded DNA-binding protein 1 (hSSB1) plays an important role in the DNA damage response and the maintenance of genomic stability. It has been shown that the core hSSB1 complex contains hSSB1, INTS3 and C9orf80. Using protein affinity purification, we have identified integrator complex subunit 6 (INTS6) as a major subunit of the core hSSB1 complex. INTS6 forms a stable complex with INTS3 and hSSB1 both in vitro and in vivo. In this complex, INTS6 directly interacts with INTS3. In response to the DNA damage response, along with INTS3 and hSSB1, INTS6 relocates to the DNA damage sites. Moreover, the hSSB1-INTS complex regulates the accumulation of RAD51 and BRCA1 at DNA damage sites and the correlated homologous recombination.
人单链 DNA 结合蛋白 1（hSSB1）在 DNA 损伤反应和维持基因组稳定性中发挥重要作用。已经表明，核心 hSSB1 复合物包含 hSSB1、INTS3 和 C9orf80。使用蛋白质亲和纯化，我们已鉴定出整合酶复合物亚基 6（INTS6）为核心 hSSB1 复合物的主要亚基。INTS6 在体外和体内均与 INTS3 和 hSSB1 形成稳定的复合物。在该复合物中，INTS6 直接与 INTS3 相互作用。在 DNA 损伤反应中，INTS6 与 INTS3 和 hSSB1 一起重新定位到 DNA 损伤部位。此外，hSSB1-INTs 复合物调节 RAD51 和 BRCA1 在 DNA 损伤部位的积累以及相关的同源重组。
