Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination.
basic_science · Level V
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- Record sourced from PubMed, PMID 18316726.
- Also identified by DOI 10.1073/pnas.0800563105 and PMC identifier 2268824.
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Abstract
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.
Medical subject headings
- DNA-Binding Proteins
- Polyubiquitin
- Proliferating Cell Nuclear Antigen
- Transcription Factors
- Ubiquitin-Protein Ligases
- Ubiquitination