Abstract 2034 Integrative Modeling of ASCC2 CUE:K63 Ub2 Interaction to Determine the Structural Basis of Specificity

DNA damage poses a threat to genomic stability and necessitates the multitude of repair mechanisms present in the cell. DNA alkylation damage such as 1-methyladenosine and 3-methylcytosine is repaired by the ALKBH3-Activating Signal Cointegrator Complex (ALKBH3-ASCC) by a mechanism in which the ASCC2 subunit targets the complex by binding to K63-linked polyubiquitin chains assembled at damage sites. The coupling of ubiquitin conjugation to endoplasmic reticulum degradation (CUE) binding domain of the ASCC2 protein exhibits a distinctive specificity for K63-linked polyubiquitin chains, setting it apart from other CUE domains that have been previously characterized in other ubiquitin-binding proteins.