Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination.

Human helicase-like transcription factor (HLTF) is frequently inactivated in colorectal and gastric cancers. Here, we show that HLTF is a functional homologue of yeast Rad5 that promotes error-free replication through DNA lesions. HLTF and Rad5 share the same unique structural features, including a RING domain embedded within a SWI/SNF helicase ...
domain and an HIRAN domain. We find that inactivation of HLTF renders human cells sensitive to UV and other DNA-damaging agents and that HLTF complements the UV sensitivity of a rad5Delta yeast strain. Also, similar to Rad5, HLTF physically interacts with the Rad6-Rad18 and Mms2-Ubc13 ubiquitin-conjugating enzyme complexes and promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen at its Lys-164 residue. A requirement of HLTF for error-free postreplication repair of damaged DNA is in keeping with its cancer-suppression role.
Mesh Terms:
Adenosine Triphosphatases, Cell Line, DNA Helicases, DNA-Binding Proteins, Drug Resistance, Genetic Complementation Test, Humans, Ligases, Lysine, Methyl Methanesulfonate, Mutation, Polyubiquitin, Proliferating Cell Nuclear Antigen, Protein Binding, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination, Ultraviolet Rays
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 11, 2008
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