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Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3768-73. doi: 10.1073/pnas.0800563105. Epub 2008 Mar 3.

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

Author information

  • 1Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvari Körút 62, H-6726, Szeged, Hungary.

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.

PMID:
18316726
[PubMed - indexed for MEDLINE]
PMCID:
PMC2268824
Free PMC Article

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