Chromodomain helicase DNA-binding protein 2 affects the repair of X-ray and UV-Induced DNA damage

Eukaryotic cells have evolved a variety of parallel and redundant DNA damage response pathways that function in a coordinated fashion to prevent the fixation of DNA damage as mutations. Despite the wealth of knowledge on DNA damage signaling on downstream cellular events, the mechanisms of DNA damage recognition, DNA repair as well as DNA damage signaling in the context of chromatin is poorly understood. Chromodomain helicase DNA-binding proteins (CHD) belong to a group of highly conserved chromatin remodeling proteins that are implicated in regulation of transcription. In an effort to understand the physiological role of one of the CHD members in a mammalian model system, we developed a mutant mouse model for the Chd2 gene. The Chd2 mutant mice are highly susceptible to spontaneous lymphoid tumor formation. In this study, we present evidence that the Chd2 mutant cells are defective in their ability to repair DNA damage induced by ionizing and ultraviolet radiation. Consistent with the role of Chd2 in regulating DNA damage responses, the Chd2 mutant cells are also sensitive to DNA damaging agents in clonogenic assays. In summary, our data suggest that the Chd2 protein is involved in regulating the DNA damage responses at the chromatin level. Environ. Mol. Mutagen. 2012. (C) 2011 Wiley Periodicals, Inc.