title: The DNA-binding box of human SPARTAN contributes to the targeting of Polη to DNA damage sites.
abstract: Inappropriate repair of UV-induced DNA damage results in human diseases such as Xeroderma pigmentosum (XP), which is associated with an extremely high risk of skin cancer. A variant form of XP is caused by the absence of Polη, which is normally able to bypass UV-induced DNA lesions in an error-free manner. However, Polη is highly error prone when replicating undamaged DNA and, thus, the regulation of the proper targeting of Polη is crucial for the prevention of mutagenesis and UV-induced cancer formation. Spartan is a novel regulator of the damage tolerance pathway, and its association with Ub-PCNA has a role in Polη targeting; however, our knowledge about its function is only rudimentary. Here, we describe a new biochemical property of purified human SPARTAN by showing that it is a DNA-binding protein. Using a DNA binding mutant, we provide in vivo evidence that DNA binding by SPARTAN regulates the targeting of Polη to damage sites after UV exposure, and this function contributes highly to its DNA-damage tolerance function.
authors.affiliation: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Agnes
authors.initials: A
authors.lastname: Toth
authors.affiliation: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Lili
authors.initials: L
authors.lastname: Hegedus
authors.affiliation: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Juhasz
authors.affiliation: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Haracska
authors.affiliation: Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary. Electronic address: burkovics.peter@brc.mta.hu.
authors.forename: Peter
authors.initials: P
authors.lastname: Burkovics
mesh_terms: D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; C574636:SPRTN protein, human; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases
keywords: DNA polymerase eta; Damage tolerance; SPARTAN; Translesion synthesis