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


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.

SUBMITTER: Unk I 

PROVIDER: S-EPMC2268824 | biostudies-other | 2008 Mar

REPOSITORIES: biostudies-other

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

Unk Ildiko I   Hajdú Ildikó I   Fátyol Károly K   Hurwitz Jerard J   Yoon Jung-Hoon JH   Prakash Louise L   Prakash Satya S   Haracska Lajos L  

Proceedings of the National Academy of Sciences of the United States of America 20080303 10


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  ...[more]

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