RAD18-dependent recruitment of SNM1A to DNA repair complexes by a ubiquitin-binding zinc finger.
SNM1A is a member of the SNM1 family of nucleases required for cellular processing of interstrand DNA crosslinks (ICLs). Little is known about the molecular function of SNM1A, in terms of its recruitment to ICL lesions or its DNA damage processing activity. Here we show that SNM1A contains a functional PIP box (PCNA-interacting protein box) and a UBZ (ubiquitin binding zinc finger), required for assembly of SNM1A into nuclear focus. Moreover, RAD18-dependent monoubiquitination of PCNA is required for Mitomycin C and Ultraviolet Light inducible SNM1A nuclear focus assembly. Taken together, our results identify a novel RAD18-PCNA(Ub)-SNM1A pathway required for nuclear focus formation and ICL resistance.
Yang
Kailin
K
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Moldovan
George-Lucian
GL
D'Andrea
Alan D
AD
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000378:metabolism; D005090:Exodeoxyribonucleases; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases; D014466:Ultraviolet Rays; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C485954:RAD18 protein, human; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D016685:Mitomycin; D044767:Ubiquitin-Protein Ligases; C493741:DCLRE1B protein, human; D003851:Deoxyribonucleases; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes
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