School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8002, Japan.
Graduate School of Medical Life Sciences, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Acta Crystallogr D Struct Biol. 2020 Aug 1;76(Pt 8):729-735. doi: 10.1107/S2059798320008074. Epub 2020 Jul 27.
HLTF (helicase-like transcription factor) is a yeast RAD5 homolog that is found in mammals. HLTF has E3 ubiquitin ligase and DNA helicase activities, and is a pivotal protein in template-switched DNA synthesis that allows DNA replication to continue even in the presence of DNA damage by utilizing a newly synthesized undamaged strand as a template. In addition, HLTF has a DNA-binding domain termed HIRAN (HIP116 and RAD5 N-terminal). HIRAN has been hypothesized to play a role in DNA binding; however, the structural basis of its role in DNA binding has remained unclear. In the past five years, several crystal structures of HIRAN have been reported. These structures revealed new insights into the molecular mechanism underlying DNA binding by HIRAN. Here, the structural information on HIRAN is summarized and the function of HIRAN in recognizing the 3'-terminus of the daughter strand at a stalled replication fork and the implications for its involvement in fork regression are discussed.
HLTF（解旋酶样转录因子）是一种在哺乳动物中发现的酵母 RAD5 同源物。HLTF 具有 E3 泛素连接酶和 DNA 解旋酶活性，是模板切换 DNA 合成中的关键蛋白，即使在存在 DNA 损伤的情况下，它也能利用新合成的未损伤链作为模板继续进行 DNA 复制。此外，HLTF 具有一个称为 HIRAN（HIP116 和 RAD5 N 端）的 DNA 结合域。据推测，HIRAN 在 DNA 结合中发挥作用；然而，其在 DNA 结合中的结构基础仍不清楚。在过去的五年中，已经报道了几个 HIRAN 的晶体结构。这些结构为 HIRAN 介导的 DNA 结合的分子机制提供了新的见解。在这里，总结了 HIRAN 的结构信息，并讨论了 HIRAN 在识别停滞复制叉处子链 3'末端以及其参与叉回归中的作用。
