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Fanconi anemia is a heritable, recessive genetic disorder, characterized on a cellular level by the inability to repair DNA interstrand crosslinks. Interstrand crosslinks are a type of DNA damage caused by both endogenous agents and exogenous chemicals, including several common chemotherapy drugs. ICLs are repaired by the Fanconi anemia pathway, which is defective in patients with the disease. The most recently discovered protein in the Fanconi anemia pathway is SLX4 (FANCP), a multidomain protein scaffold that also has Holliday junction resolvase activity. One of several domains of SLX4 consists of two tandem ubiquitin-binding Zinc finger (UBZ) domains, which are known to bind to K63-linked ubiquitin chains in vitro. We have attempted to identify whether SLX4 interacts with ubiquitylated γ-H2AX or PCNA through its UBZ domains, and concluded that the ubiquitin ligase UBC13 may be necessary for interstrand crosslink repair, and that its activity may be necessary for SLX4 localization. We also observed ubiquitin-like post-translational modifications on several truncated fragments of SLX4, and thus attempted to characterize this modification.
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Spitz, Gabriella, "A Characterization of the Ubiquitin-Binding Zinc Finger (UBZ) Domains of SLX4 and their Role in the Fanconi Anemia Pathway" (2012). Senior Projects Spring 2012. 93.