Mdt1/ASCIZ: A new DNA damage response protein family

Abstract

DNA damage response pathways are crucial for genome stability and prevention of cancer, and are overall remarkably conserved from yeast to mammals. Two novel DNA damage response proteins, yeast Mdt1 (Modifier of DNA damage tolerance 1) and human ASCIZ (ATM/ATR-substrate Chk2-interacting Zn2+-finger protein), were recently identified based on their interactions with the N-terminal FHA domains of the conserved checkpoint kinases Rad53 and Chk2, respectively, and ASCIZ was subsequently re-isolated as an ATM-interacting protein (ATMIN). Mdt1 and ASCIZ share remarkable sequence similarity (36% highly conserved residues, 17% identity) and extended SQ/TQ cluster domains (SCDs) typical of DNA damage..