title: The Fanconi anaemia components UBE2T and FANCM are functionally linked to nucleotide excision repair.
abstract: The many proteins that function in the Fanconi anaemia (FA) monoubiquitylation pathway initiate replicative DNA crosslink repair. However, it is not clear whether individual FA genes participate in DNA repair pathways other than homologous recombination and translesion bypass. Here we show that avian DT40 cell knockouts of two integral FA genes--UBE2T and FANCM are unexpectedly sensitive to UV-induced DNA damage. Comprehensive genetic dissection experiments indicate that both of these FA genes collaborate to promote nucleotide excision repair rather than translesion bypass to protect cells form UV genotoxicity. Furthermore, UBE2T deficiency impacts on the efficient removal of the UV-induced photolesion cyclobutane pyrimidine dimer. Therefore, this work reveals that the FA pathway shares two components with nucleotide excision repair, intimating not only crosstalk between the two major repair pathways, but also potentially identifying a UBE2T-mediated ubiquitin-signalling response pathway that contributes to nucleotide excision repair.
authors.affiliation: Scottish Institute for Cell Signalling, University of Dundee, Dundee, United Kingdom.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Kelsall
authors.forename: Judith
authors.initials: J
authors.lastname: Langenick
authors.forename: Craig
authors.initials: C
authors.lastname: MacKay
authors.forename: Ketan J
authors.initials: KJ
authors.lastname: Patel
authors.forename: Arno F
authors.initials: AF
authors.lastname: Alpi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002645:Chickens; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism; D059765:Homologous Recombination; D015398:Signal Transduction / Q000502:physiology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D004265:DNA Helicases