Topic
HLTF
About: HLTF is a research topic. Over the lifetime, 129 publications have been published within this topic receiving 5001 citations. The topic is also known as: HIP116 & HIP116A.
Papers published on a yearly basis
Papers
TL;DR: The results suggest that HLTF and SHPRH are functional homologues of yeast Rad5 that cooperatively mediate PCNA polyubiquitination and maintain genomic stability.
Abstract: Chronic stalling of DNA replication forks caused by DNA damage can lead to genomic instability. Cells have evolved lesion bypass pathways such as postreplication repair (PRR) to resolve these arrested forks. In yeast, one branch of PRR involves proliferating cell nuclear antigen (PCNA) polyubiquitination mediated by the Rad5-Ubc13-Mms2 complex that allows bypass of DNA lesion by a template-switching mechanism. Previously, we identified human SHPRH as a functional homologue of yeast Rad5 and revealed the existence of RAD5-like pathway in human cells. Here we report the identification of HLTF as a second RAD5 homologue in human cells. HLTF, like SHPRH, shares a unique domain architecture with Rad5 and promotes lysine 63-linked polyubiquitination of PCNA. Similar to yeast Rad5, HLTF is able to interact with UBC13 and PCNA, as well as SHPRH; and the reduction of either SHPRH or HLTF expression enhances spontaneous mutagenesis. Moreover, Hltf-deficient mouse embryonic fibroblasts show elevated chromosome breaks and fusions after methyl methane sulfonate treatment. Our results suggest that HLTF and SHPRH are functional homologues of yeast Rad5 that cooperatively mediate PCNA polyubiquitination and maintain genomic stability.
287 citations
TL;DR: It is found 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.
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 cancer-suppression role.
250 citations
TL;DR: It is suggested that HLTF is a candidate colon cancer suppressor gene and a common target for methylation and epigenetic gene silencing in colon cancer and HLTF methylation was detected in 27 of 63 cases.
Abstract: Chromatin remodeling enzymes are increasingly implicated in a variety of important cellular functions. Various components of chromatin remodeling complexes, including several members of the SWI/SNF family, have been shown to be disrupted in cancer. In this study we identified as a target for gene inactivation in colon cancer the gene for helicase-like transcription factor (HLTF), a SWI/SNF family protein. Loss of HLTF expression accompanied by HLTF promoter methylation was noted in nine of 34 colon cancer cell lines. In these cell lines HLTF expression was restored by treatment with the demethylating agent 5-azacytidine. In further studies of primary colon cancer tissues, HLTF methylation was detected in 27 of 63 cases (43%). No methylation of HLTF was detected in breast or lung cancers, suggesting selection for HLTF methylation in colonic malignancies. Transfection of HLTF suppressed 75% of colony growth in each of three different HLTF-deficient cell lines, but showed no suppressive effect in any of three HLTF-proficient cell lines. These findings show that HLTF is a common target for methylation and epigenetic gene silencing in colon cancer and suggest HLTF is a candidate colon cancer suppressor gene.
198 citations
TL;DR: In this paper, the HIRAN domain is found to be a modified oligonucleotide/oligosaccharide (OB) fold that binds to 3' ssDNA ends.
195 citations
TL;DR: It is shown that HLTF and SHPRH suppress mutagenesis in a damage-specific manner, preventing mutations induced by UV and MMS, respectively.
186 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 4 |
| 2020 | 6 |
| 2019 | 7 |
| 2018 | 11 |
| 2017 | 4 |
| 2016 | 10 |