Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation
Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation
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DOI：
10.1074/jbc.274.48.34337
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发表时间：
1999-11-26
影响因子：
4.8
通讯作者：
Akhmedov, AT
中科院分区：
文献类型：
--
作者：
Baechtold, H;Kuroda, M;Akhmedov, AT
同源重组在 DNA 双链断裂修复中发挥着重要作用。此前，我们检测到两种大小为 100 和 75 kDa 的哺乳动物核蛋白（分别为 POMp100 和 POMp75），它们能够促进同源 DNA 配对，这是同源重组的关键步骤。在这里，我描述了人类 (h) POMp75 作为原癌蛋白 TLS/FUS 的鉴定，hPOMp75/TLS 结合单链和双链 DNA，并介导互补 DNA 链的退火。更重要的是，它促进单链寡核苷酸摄取到同源超螺旋DNA中形成D环。 D环的形成是通过重组修复DNA双链断裂的重要步骤。 hPOMp75/TLS 催化的 DNA 退火和 D 环形成需要 Mg2+，并且不依赖于 ATP。有趣的是，致癌融合形式 TLS-CHOP 不能促进 DNA 配对。这些数据表明 hPOMp75/TLS 在维持基因组完整性方面可能发挥作用。
Homologous recombination plays a fundamental role in DNA double-strand break repair. Previously, we detected two mammalian nuclear proteins of 100 and 75 kDa (POMp100 and POMp75, respectively) that are able to promote homologous DNA pairing, a key step in homologous recombination. Here me describe the identification of human (h) POMp75 as the pro-oncoprotein TLS/FUS, hPOMp75/TLS binds both single- and double-stranded DNAs and mediates annealing of complementary DNA strands. More important, it promotes the uptake of a single-stranded oligonucleotide into a homologous superhelical DNA to form a D-loop. The formation of a D-loop is an essential step in DNA double-strand break repair through recombination. DNA annealing and D-loop formation catalyzed by hPOMp75/TLS require Mg2+ and are ATP-independent. Interestingly, the oncogenic fusion form TLS-CHOP is not able to promote DNA pairing. These data suggest a possible role for hPOMp75/TLS in maintenance of genomic integrity.