A Breathtaking Phenotype: Unexpected Roles of the DNA Base Damage Response Protein ASCIZ as a Key Regulator of Early Lung Development

Cell Cycle. 2011 Apr 15;10(8):1222-4. doi: 10.4161/cc.10.8.15336. Epub 2011 Apr 15.


The ATM substrate Chk2-interacting Zn(2+)-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/ß-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 efficiency factor for DNA base damage repair as well as a key transcriptional regulator of early lung development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • DNA Damage
  • DNA Methylation
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression
  • Genetic Association Studies
  • Lung / embryology
  • Lung / metabolism
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Organogenesis / genetics*
  • Phenotype
  • Pregnancy
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction / genetics
  • Transcription Factors
  • Transcription, Genetic
  • Transcriptional Activation*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • ATMIN protein, mouse
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ataxia Telangiectasia Mutated Proteins
  • Atm protein, mouse
  • Protein-Serine-Threonine Kinases