Sulfotransferase (SULT) function has been well studied in healthy human subjects by quantifying mRNA and protein expression and determining enzyme activity with probe substrates.

Fanconi anemia (FA) is a rare genetic disease characterized by congenital defects, bone marrow failure and cancer susceptibility. FA is caused by biallelic mutations in any one of fifteen genes. The FA proteins function in the FA‐BRCA pathway to repair DNA damage and to prevent cellular transformation. A hallmark of FA patient cells is increased sensitivity to DNA interstrand crosslinking agents such as mitomycin C (MMC). A key step in the activation of this pathway is the monoubiquitination of the FANCD2 and FANCI proteins, which targets these proteins to chromatin. Following exposure to DNA damaging agents, histones are subject to posttranslational modification, e.g. acetylation, resulting in chromatin remodeling, facilitating the recruitment of DNA repair proteins to sites of DNA damage. In this study, we report that inhibition of class I and II, but not class III, histone deacetylases leads to a failure to activate the monoubiquitination of FANCD2 and FANCI following exposure to MMC. This leads to increased sensitivity to the cytotoxic and clastogenic effects of MMC. In addition, we describe the identification and characterization of a putative FANCD2 H4 binding domain. Interestingly, mutation of this domain leads to polyubiquitination of FANCD2. Together our preliminary results suggest that activation of the FA‐BRCA pathway is dependent upon the deacetylation of histones and on interaction with histone H4.