Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination
Year: 2008
Type: article
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.
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Howard Hughes Medical Institute, Wellcome Trust, Hungarian Scientific Research Fund, Nemzeti Kutatási és Technológiai Hivatal, Hungarian Science Foundation, National Institutes of Health, Medical Research Council, National Cancer Institute, National Institute of Environmental Health Sciences
OpenAlex ID: W2073294832