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

Ildiko Unk, Ildikó Hajdú, Károly Fátyol, Jerard Hurwitz, Jung Hoon Yoon, Louise Prakash, Satya Prakash, Lajos Haracska

Research output: Contribution to journalArticle

143 Scopus citations

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 rad5Δ 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 cancersuppression role.

Original languageEnglish (US)
Pages (from-to)3768-3773
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number10
DOIs
StatePublished - Mar 25 2008

Keywords

  • Damage bypass
  • K63 polyubiquitination
  • Tumor suppressor
  • Yeast Rad5

ASJC Scopus subject areas

  • General

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