HLTF (helicase-like transcription factor)

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URI: http://hdl.handle.net/2042/68527  |   DOI : https://doi.org/10.4267/2042/68527
Title: HLTF (helicase-like transcription factor)
Author: Dhont, Ludovic; Belayew, Alexandra
Abstract: HLTF is a transcription factor - The HLTF; Transcription factor; Post-replication DNA Repair; DNA damage tolerance pathways; E3-ubiquitin ligase; Cell Cycle; Cancer; Epigenetics; promoter methylation; Alternative splicing.Helicase-Like Transcription Factor (HLTF/SMARCA3) belongs to the family of SWI/SNF proteins that use the energy of ATP hydrolysis to remodel chromatin in a variety of cellular processes. Several groups independently isolated HLTF through its capacity to selectively interact with a DNA cis-element in the promoter or enhancer of different genes involved in cardiac development during embryogenesis, cell cycle, collagen biogenesis, cell motility and angiogenesis. HLTF is a key element in DNA Damage Tolerance pathways - HLTF plays a role in DNA Damage Tolerance, especially in (i) translesion synthesis and (ii) template switching pathways (fork regression and strand invasion). HLTF is an E3 ubiquitin ligase targeting PCNA (K164) that results in DTT activation. The E3 ubiquitin ligase, translocase and HIRAN catalytic domain are the HLTF core activities. A key role in DNA repair was confirmed in vivo, in 2 different Hltf null mouse models and showed that Hltf loss compromises error-free DNA replication and modulates mutagenesis by regulating proteins involved in the G2/M phase transition of the cell cycle in mouse heart and brain. HLTF is a tumor suppressor gene - In cancer, two mechanisms of HLTF inactivation are reported: (i) hypermethylation of its promoter and (ii) expression of truncated protein forms that have lost domains involved in DNA repair. These data support a role of tumor suppressor gene for HLTF. The first association between HLTF inactivation and tumorigenesis was shown when hypermethylation of the HLTF promoter was detected in 43% of primary colon tumors and 22-55% of gastric cancers. Moreover, HLTF deficiency in Apc-/+ mice induced the transition from colon adenocarcinoma to a carcinoma with high chromosomal instability. In head and neck, thyroid and uterus (cervix) cancers, an increased expression of two HLTF protein forms truncated in the carboxyl-terminal domain following alternative mRNA splicing was reported. These truncated HLTF forms have lost their DNA repair ability and might also have gained functions favouring cancer.
Subject: HLTF; Transcription factor; Post-replication DNA Repair; DNA damage tolerance pathways; E3-ubiquitin ligase; Cell Cycle; Cancer; Epigenetics; promoter methylation; Alternative splicing; Genes Section; Adaptor Proteins, Signal Transducing/genetics; Animals; Apoptosis Regulatory Proteins/genetics; Azoxymethane; Calcium-Calmodulin-Dependent Protein Kinases/genetics; Cell Adhesion Molecule-1; Cell Adhesion Molecules; Colonic Neoplasms/chemically induced/*genetics; Connexins/genetics; Cyclin-Dependent Kinase Inhibitor p16/genetics; *DNA Methylation; DNA Modification Methylases/genetics; DNA Repair Enzymes/genetics; DNA-Binding Proteins/genetics; Death-Associated Protein Kinases
Publisher: ARMGHM - Atlas Génétique des Cancers
Date: 2017

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