Crystal structure of HIRAN domain involved in DNA damage tolerance

Abstract

  DNA damage tolerance (DDT) is a cell function to release replication blockage caused by DNA damage and to continue DNA synthesis even in the presence of DNA damage. DDT includes two pathways, translesion and template-switched DNA syntheses. Helicase-like transcription factor (HLTF) is a central protein in the template-switched DNA synthesis pathway, in which one newly synthesized strand is utilized as an undamaged template for replication. HLTF consists of three domains, N-terminal DNA binding, DNA helicase, and ubiquitin ligase domains. The N-terminal DNA binding domain is termed HIRAN domain. Here, we outline the crystal structure of HIRAN domain bound to DNA and its functional implication in template-switched DNA synthesis. Furthermore, we describe that artifacts in crystallization gave fruitful results in our structural study of HIRAN domain.