A breathtaking phenotype: unexpected roles of the DNA base damage response protein ASCIZ as a key regulator of early lung development.

The ATM substrate Chk2-interacting Zn2+-finger protein (ASCIZ, also known as ATMIN and ZNF822) has previously been reported to be important for the repair of methylating and oxidative DNA damage, and it has also been proposed to regulate the stability and DNA damage-independent activation of the ATM kinase. While the role of the protein in the regulation of ATM remains controversial, two recent ASCIZ mouse knockout papers confirm its role in the DNA base damage response, including oxidative stress resistance in vivo. Similar to other DNA base damage repair proteins, ASCIZ is essential for embryonic development, with lethality of Asciz-null embryos around day E16.5 post conception. Unexpectedly, absence of ASCIZ also leads to severe organ development defects, most notably, complete absence of lungs similar to mutants in Wnt2-2b/s-catenin and FGF10/FGFR2b signalling pathways. Together with evidence that ASCIZ can activate transcription in vitro, the phenotype indicates that ASCIZ has dual functions as an ef...