For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
40
views
13
references
 Top references
cited by
9
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      2
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Rad5, HLTF, and SHPRH: A Fresh View of an Old Story

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Not only have helicase-like transcription factor (HLTF) and SNF2 histone-linker PHD-finger RING-finger helicase (SHPRH) proved to be important players in post-replication repair like their yeast counterpart, Rad5, but they are also involved in multiple biological functions and are associated with several human disorders. We provide here an updated view of their functions, associated diseases, and potential therapeutic approaches.

          Related collections

          Most cited references13

          • Record: found
          • Abstract: found
          • Article: not found

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

          Karoly Fatyol, Ildiko Unk, Satya Prakash … (2008)
          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.
          Article 0 comments Cited 93 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen.

            Karoly Fatyol, Ildiko Unk, Barnabas Szakal … (2006)
            Human SHPRH gene is located at the 6q24 chromosomal region, and loss of heterozygosity in this region is seen in a wide variety of cancers. SHPRH is a member of the SWI/SNF family of ATPases/helicases, and it possesses a C(3)HC(4) RING motif characteristic of ubiquitin ligase proteins. In both of these features, SHPRH resembles the yeast Rad5 protein, which, together with Mms2-Ubc13, promotes replication through DNA lesions via an error-free postreplicational repair pathway. Genetic evidence in yeast has indicated a role for Rad5 as a ubiquitin ligase in mediating the Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Here we show that SHPRH is a functional homolog of Rad5. Similar to Rad5, SHPRH physically interacts with the Rad6-Rad18 and Mms2-Ubc13 complexes, and we show that SHPRH protein is a ubiquitin ligase indispensable for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Based on these observations, we predict a role for SHPRH in promoting error-free replication through DNA lesions. Such a role for SHPRH is consistent with the observation that this gene is mutated in a number of cancer cell lines, including those from melanomas and ovarian cancers, which raises the strong possibility that SHPRH function is an important deterrent to mutagenesis and carcinogenesis in humans.
            Article 0 comments Cited 79 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Role of double-stranded DNA translocase activity of human HLTF in replication of damaged DNA.

              Ildiko Unk, András Blastyák, Ildiko Hajdu … (2010)
              Unrepaired DNA lesions can block the progression of the replication fork, leading to genomic instability and cancer in higher-order eukaryotes. In Saccharomyces cerevisiae, replication through DNA lesions can be mediated by translesion synthesis DNA polymerases, leading to error-free or error-prone damage bypass, or by Rad5-mediated template switching to the sister chromatid that is inherently error free. While translesion synthesis pathways are highly conserved from yeast to humans, very little is known of a Rad5-like pathway in human cells. Here we show that a human homologue of Rad5, HLTF, can facilitate fork regression and has a role in replication of damaged DNA. We found that HLTF is able to reverse model replication forks, a process which depends on its double-stranded DNA translocase activity. Furthermore, from analysis of isolated dually labeled chromosomal fibers, we demonstrate that in vivo, HLTF promotes the restart of replication forks blocked at DNA lesions. These findings suggest that HLTF can promote error-free replication of damaged DNA and support a role for HLTF in preventing mutagenesis and carcinogenesis, providing thereby for its potential tumor suppressor role.
              Article 0 comments Cited 73 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Sherif F. El-Khamisy
                Journal
                Journal ID (nlm-ta): Trends Genet
                Journal ID (iso-abbrev): Trends Genet
                Title: Trends in Genetics
                Publisher: Elsevier Trends Journals
                ISSN (Print): 0168-9525
                Publication date PMC-release: 1 August 2018
                Publication date (Print): August 2018
                Volume: 34
                Issue: 8
                Pages: 574-577
                Affiliations
                [1 ]Krebs Institute, Department of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, Sheffield S10 2TN, UK
                [2 ]Center for Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza 12578, Egypt
                [3 ]These authors contributed equally to the manuscript
                Author notes
                Article
                Publisher ID: S0168-9525(18)30082-9
                DOI: 10.1016/j.tig.2018.04.006
                PMC ID: 6055012
                PubMed ID: 29807746
                SO-VID: fcef85d7-f577-427b-91ed-fc83a81b8b1b
                Copyright © © 2018 The Author(s)
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Genetics
                Keywords: rad5,hltf,shprh,cancer,hiv-1,bowel disease
                Data availability:
                ScienceOpen disciplines: Genetics
                Keywords: rad5, hltf, shprh, cancer, hiv-1, bowel disease

                Comments

                Comment on this article

                scite_

                Similar content2

                See all similar

                Cited by9

                See all cited by

                Most referenced authors126

                See all reference authors