The DNA-binding box of human SPARTAN contributes to the targeting of Poleta to DNA damage sites

Tóth, Ágnes and Döme, Lili and Juhász, Szilvia and Haracska, Lajos and Burkovics, Péter (2017) The DNA-binding box of human SPARTAN contributes to the targeting of Poleta to DNA damage sites. DNA REPAIR, 49. pp. 33-42. ISSN 1568-7864

Preview

Text TothDNARepairmanu.pdf Download (15MB) | Preview

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 Poleta, which is normally able to bypass UV-induced DNA lesions in an error-free manner. However, Poleta is highly error prone when replicating undamaged DNA and, thus, the regulation of the proper targeting of Poleta 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 Poleta 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 Poleta to damage sites after UV exposure, and this function contributes highly to its DNA-damage tolerance function.

Actions (login required)

Edit Item