Genomes and Genes
Gene Symbol: SLX4
Description: SLX4 structure-specific endonuclease subunit
Alias: BTBD12, FANCP, MUS312, structure-specific endonuclease subunit SLX4, BTB/POZ domain-containing protein 12
- Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repairJennifer M Svendsen
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Cell 138:63-77. 2009..Here, we identify BTBD12 as the human ortholog of the budding yeast DNA repair factor Slx4p and D. melanogaster MUS312...
- Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombinationSabrina L Andersen
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA
Mol Cell 35:128-35. 2009..protein-protein interactions, and ICL repair function, we determined that the mammalian ortholog of MUS312 is BTBD12. Orthology between these proteins and S...
- Human GEN1 and the SLX4-associated nucleases MUS81 and SLX1 are essential for the resolution of replication-induced Holliday junctionsElizabeth Garner
Laboratory of Genome Maintenance, The Rockefeller University, New York, NY 10065, USA
Cell Rep 5:207-15. 2013..In vitro, HJs may be nucleolytically processed by MUS81-EME1, GEN1, and SLX4-SLX1. Here, we exploit human SLX4-null cells to examine the requirements for HJ resolution in vivo...
- Coordinated actions of SLX1-SLX4 and MUS81-EME1 for Holliday junction resolution in human cellsHaley D M Wyatt
London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
Mol Cell 52:234-47. 2013..Here, we show that three structure-selective endonucleases, namely SLX1-SLX4, MUS81-EME1, and GEN1, define two pathways of HJ resolution in human cells...
- SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeresBingbing Wan
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China Howard Hughes Medical Institute, University of Michigan Medical School, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA Department of Biological Chemistry, University of Michigan Medical School, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA
Cell Rep 4:861-9. 2013b>SLX4 interacts with several endonucleases to resolve structural barriers in DNA metabolism. SLX4 also interacts with telomeric protein TRF2 in human cells. The molecular mechanism of these interactions at telomeres remains unknown...
- Localization-dependent and -independent roles of SLX4 in regulating telomeresJamie S J Wilson
MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
Cell Rep 4:853-60. 2013b>SLX4, a scaffold for structure-specific DNA repair nucleases, is important for several types of DNA repair...
- Regulation of multiple DNA repair pathways by the Fanconi anemia protein SLX4Yonghwan Kim
Laboratory of Genome Maintenance, Rockefeller University, New York, NY 10065 6399, USA
Blood 121:54-63. 2013SLX4, the newly identified Fanconi anemia protein, FANCP, is implicated in repairing DNA damage induced by DNA interstrand cross-linking (ICL) agents, topoisomerase I (TOP1) inhibitors, and in Holliday junction resolution...
- Mutation analysis of the SLX4/FANCP gene in hereditary breast cancerRosa Landwehr
Clinics of Obstetrics and Gynaecology, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
Breast Cancer Res Treat 130:1021-8. 2011b>SLX4 coordinates three structure-specific endonucleases in the DNA damage response. One subtype of Fanconi anaemia, FA-P, has recently been attributed to biallelic SLX4 gene mutations...
- SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtypeChantal Stoepker
Department of Clinical Genetics, Vrije Universiteit VU Medical Center, Amsterdam, The Netherlands
Nat Genet 43:138-41. 2011..b>SLX4, which coordinates three separate endonucleases, was recently recognized as an important regulator of DNA repair...
- Mutations of the SLX4 gene in Fanconi anemiaYonghwan Kim
Laboratory of Genome Maintenance, The Rockefeller University, New York, New York, USA
Nat Genet 43:142-6. 2011..anemia and show that the cellular defects in these individuals' cells are complemented by wildtype SLX4, demonstrating that biallelic mutations in SLX4 (renamed here as FANCP) cause a new subtype of Fanconi anemia, Fanconi anemia-P.
- Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repairIvan M Munoz
MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
Mol Cell 35:116-27. 2009Budding yeast Slx4 interacts with the structure-specific endonuclease Slx1 to ensure completion of ribosomal DNA replication...
- Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleasesSamira Fekairi
Genome Instability and Carcinogenesis UPR3081 CNRS, Conventionné par l Université d Aix Marseille 2, IGC, IMM 31 chemin Joseph Aiguier, 13402 Marseille, France
Cell 138:78-89. 2009..Here we report the identification of Slx4 orthologs in metazoa, including fly MUS312, essential for meiotic recombination, and human BTBD12, an ATM/ATR checkpoint kinase substrate...
- Noncovalent interactions with SUMO and ubiquitin orchestrate distinct functions of the SLX4 complex in genome maintenanceJian Ouyang
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Mol Cell 57:108-22. 2015b>SLX4, a coordinator of multiple DNA structure-specific endonucleases, is important for several DNA repair pathways...
- Distinct functional roles for the two SLX4 ubiquitin-binding UBZ domains mutated in Fanconi anemiaChristophe Lachaud
MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, UK
J Cell Sci 127:2811-7. 2014Defects in SLX4, a scaffold for DNA repair nucleases, result in Fanconi anemia (FA), due to the defective repair of inter-strand DNA crosslinks (ICLs)...
- DNA damage repair machinery and HIV escape from innate immune sensingChristelle Brégnard
Laboratoire de Virologie Moleculaire, Institut de Génétique Humaine CNRS UPR1142, Montpellier, France
Front Microbiol 5:176. 2014..human immunodeficiency virus (HIV), the viral auxiliary protein Vpr activates the structure-specific endonuclease SLX4 complex to promote escape from innate immune sensing and, as a side effect, induces replication stress in cycling ..
- Nuclease delivery: versatile functions of SLX4/FANCP in genome maintenanceYonghwan Kim
Department of Life Systems, Sookmyung Women s University, Seoul 140 742, Korea
Mol Cells 37:569-74. 2014As a scaffold, SLX4/FANCP interacts with multiple proteins involved in genome integrity...
- A cell cycle-regulated Slx4-Dpb11 complex promotes the resolution of DNA repair intermediates linked to stalled replicationDalia Gritenaite
DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
Genes Dev 28:1604-19. 2014..Central to this regulation is a conserved complex comprising the scaffold proteins Dpb11 and Slx4 that is under stringent control...
- Identification and characterization of MUS81 point mutations that abolish interaction with the SLX4 scaffold proteinNidhi Nair
MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
DNA Repair (Amst) 24:131-7. 2014..In metazoans, a proportion of cellular MUS81-EME1 binds the SLX4 scaffold protein, which is itself instrumental for ICL repair...
- G2/M cell cycle arrest correlates with primate lentiviral Vpr interaction with the SLX4 complexGregory Berger
Department of Infectious Diseases, Faculty of Life Sciences and Medicine, King s College London, London, United Kingdom
J Virol 89:230-40. 2015..that human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) mediates this through activation of the SLX4/MUS81/EME1 exonuclease complex that forms part of the Fanconi anemia DNA repair pathway...
- How SLX4 cuts through the mystery of HIV-1 Vpr-mediated cell cycle arrestMarie Lise Blondot
INSERM, U1016, Institut Cochin, Paris, France
Retrovirology 11:117. 2014..This study highlights for the first time how Vpr recruits the SLX4 endonuclease complex and how Vpr-induced inappropriate activation of this complex leads to G2 arrest...
- Premature activation of the SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensingNadine Laguette
Institut de Genetique Humaine, Laboratoire de Virologie Moleculaire, CNRS UPR1142, Montpellier 34000, France Electronic address
Cell 156:134-45. 2014..we show that G2/M arrest results from untimely activation of the structure-specific endonuclease (SSE) regulator SLX4 complex (SLX4com) by Vpr, a process that requires VPRBP-DDB1-CUL4 E3-ligase complex...
- The SLX4 complex is a SUMO E3 ligase that impacts on replication stress outcome and genome stabilityJean Hugues Guervilly
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7258, Inserm Unité 1068, Centre de Recherche en Cancerologie de Marseille, Institut Paoli Calmettes, F 13009 Marseille, France Aix Marseille Université, F 13284 Marseille, France Electronic address
Mol Cell 57:123-37. 2015The SLX4 Fanconi anemia protein is a tumor suppressor that may act as a key regulator that engages the cell into specific genome maintenance pathways...
- USP45 deubiquitylase controls ERCC1-XPF endonuclease-mediated DNA damage responsesAna B Pérez-Oliva
MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee, UK
EMBO J 34:326-43. 2015..Together, these results establish USP45 as a new regulator of XPF-ERCC1 crucial for efficient DNA repair. ..
- SUMOylation and PARylation cooperate to recruit and stabilize SLX4 at DNA damage sitesRomán González-Prieto
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
EMBO Rep 16:512-9. 2015..However, whether it is important for interstrand crosslink repair remains unknown. We report that the SLX4 nuclease scaffold protein is regulated by SUMOylation...
- Alterations of DNA repair genes in the NCI-60 cell lines and their predictive value for anticancer drug activityFabricio G Sousa
Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica, Programa de Pós graduação em Farmácia, Universidade Federal de Mato Grosso do Sul, Campo Grande 79070 900, MS, Brazil
DNA Repair (Amst) 28:107-15. 2015..In addition to SLFN11, the Fanconi anemia-scaffolding gene SLX4 (FANCP/BTBD12) stood out among the genes most significantly related with DNA synthesis and topoisomerase inhibitors...
- Physical interaction between SLX4 (FANCP) and XPF (FANCQ) proteins and biological consequences of interaction-defective missense mutationsKeiji Hashimoto
Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York, Stony Brook, NY 11794, USA
DNA Repair (Amst) 35:48-54. 2015SLX4 (FANCP) and XPF (FANCQ) proteins interact with each other and play a vital role in the Fanconi anemia (FA) DNA repair pathway...
- Paternal or Maternal Uniparental Disomy of Chromosome 16 Resulting in Homozygosity of a Mutant Allele Causes Fanconi AnemiaFrank X Donovan
Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland
Hum Mutat 37:465-8. 2016..FANCA and FANCP/SLX4 genes, both located on chromosome 16, were the affected recessive FA genes in three and one family ..
- Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton RadiationQi Liu
Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
Int J Radiat Oncol Biol Phys 95:78-85. 2016..We investigated the role of SLX4 (FANCP), which acts as a docking platform for the assembly of multiple structure-specific endonucleases, in the response ..
- HIV-1 Vpr-a still "enigmatic multitasker"Carolin A Guenzel
Cochin Institute, Inserm U1016, Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes Paris, France
Front Microbiol 5:127. 2014..In this review, we will summarize the main reported functions of HIV-1 Vpr and their significance in the context of the viral life cycle. ..
- From arrest to escape: HIV-1 Vpr cuts a dealEric A Cohen
Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal IRCM and Department of Microbiology, Infectiology and Immunology, Universite de Montreal, Montreal, QC H2W 1R7, Canada Electronic address
Cell Host Microbe 15:125-7. 2014..In a recent issue of Cell, Laguette et al. (2014) demonstrate that untimely activation of the structure-specific endonuclease regulator SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing.
- FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stressKasper Fugger
Biotech Research and Innovation Centre BRIC, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen N DK 2200, Denmark
Nat Commun 4:1423. 2013..Our data suggest that FBH1 helicase activity is required to eliminate cells with excessive replication stress through the generation of MUS81-induced DNA double-strand breaks...
- Low prevalence of SLX4 loss-of-function mutations in non-BRCA1/2 breast and/or ovarian cancer familiesGorka Ruiz de Garibay
Laboratorio de Oncologia Molecular, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain
Eur J Hum Genet 21:883-6. 2013..We address the role of SLX4/FANCP in breast/ovarian cancer susceptibility by conducting a comprehensive mutation scanning in 486 index cases from ..
- Analysis of the novel fanconi anemia gene SLX4/FANCP in familial breast cancer casesJanine L Bakker
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
Hum Mutat 34:70-3. 2013SLX4/FANCP is a recently discovered novel disease gene for Fanconi anemia (FA), a rare recessive disorder characterized by chromosomal instability and increased cancer susceptibility...
- The nuclease hSNM1B/Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP/SLX4Bastian Salewsky
Institute of Medical and Human Genetics, Charite Universitatsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany
Hum Mol Genet 21:4948-56. 2012..expressed hSNM1B/Apollo co-immunoprecipitates with SLX4, a protein recently identified as a new FA protein, FANCP, and known to interact with several structure-specific nucleases...
- Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesisGargi Ghosal
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
J Biol Chem 287:34225-33. 2012..Thus, C1orf124 acts at multiple steps in TLS, stabilizes RAD18 and ubiquitinated PCNA at damage sites, and facilitates the switch from replicative to TLS polymerase to bypass DNA lesion...
- Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvaseKseniya Zakharyevich
Department of Microbiology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
Cell 149:334-47. 2012..three distinct endonucleases capable of resolving JMs in vitro have been identified: Mus81-Mms4(EME1), Slx1-Slx4(BTBD12), and Yen1(GEN1)...
- Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer familiesJuana Fernández-Rodríguez
Hereditary Cancer Program, Catalan Institute of Oncology ICO, Hospital Duran i Reynals, Bellvitge Institute for Biomedical Research IDIBELL, L Hospitalet, Barcelona, Catalonia, Spain
BMC Cancer 12:84. 2012..Mutations in the SLX4 gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been ..
- Sequencing analysis of SLX4/FANCP gene in Italian familial breast cancer casesIrene Catucci
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy
PLoS ONE 7:e31038. 2012..Very recently, SLX4 has been established as a new FA gene raising the question of its implication in breast cancer risk...
- Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemiaGerry P Crossan
Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
Nat Genet 43:147-52. 2011..Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness ..
- Mammalian BTBD12 (SLX4) protects against genomic instability during mammalian spermatogenesisJ Kim Holloway
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
PLoS Genet 7:e1002094. 2011..Recent studies have implicated the fly and worm orthologs, MUS312 and HIM-18, in the regulation of meiotic crossovers arising from double-strand break (DSB) initiating events and ..
- Processing of joint molecule intermediates by structure-selective endonucleases during homologous recombination in eukaryotesErin K Schwartz
Department of Microbiology, University of California Davis, Davis, CA 95616, USA
Chromosoma 120:109-27. 2011..RuvC, leading to the discovery of a number of DNA endonucleases, including Mus81-Mms4/EME1, Slx1-Slx4/BTBD12/MUS312, XPF-ERCC1, and Yen1/GEN1...