The fork remodeler helicase-like transcription factor in cancer development: all at once.

The Helicase-like Transcription Factor (HLTF) is a member of the SNF2-family of fork remodelers, primarily studied for its capacity to provide DNA Damage Tolerance (DDT) and to induce replication fork reversal (RFR). HLTF is recruited at stalled forks where both its ATPase motor and HIP116 Rad5p N-terminal (HIRAN) domains are necessary for regulating its interaction with DNA. HIRAN bestows specificity to ssDNA 3'-end and imparts branch migration as well as DNA remodeling capabilities facilitating damage repair. Both expression regulation and mutation rate affect HLTF activity. Gene hypermethylation induces loss of HLTF function, in particular in colorectal cancer (CRC), implying a tumour suppressor role. Surprisingly, a correlation between hypermethylation and HLTF mRNA upregulation has also been observed, even within the same cancer type. In many cancers, both complex mutation patterns and the presence of gene Copy Number Variations (CNVs) have been reported. These conditions affect the amount of functional HLTF and question the physiological role of this fork remodeler. This review offers a systematic collection of the presently strewed information regarding HLTF, its structural and functional characteristics, the multiple roles in DDT and the regulation in cancer progression highlighting new research perspectives. Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Citation

Yossma Waheed, Aditya Mojumdar, Mohammad Shafiq, Ario de Marco, Matteo De March. The fork remodeler helicase-like transcription factor in cancer development: all at once. Biochimica et biophysica acta. Molecular basis of disease. 2024 Oct;1870(7):167280

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PMID: 38851303

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