Nuclear myosin 1 (NM1) has been implicated in key nuclear functions. Together with actin, it has been shown to initiate and regulate transcription, it is part of the chromatin remodeling complex B-WICH, and is responsible for rearrangements of chromosomal territories in response to external stimuli. Here we show that deletion of NM1 in mouse embryonic fibroblasts leads to chromatin and transcription dysregulation affecting the expression of DNA damage and cell cycle genes. NM1 KO cells exhibit increased DNA damage and changes in cell cycle progression, proliferation, and apoptosis, compatible with a phenotype resulting from impaired p53 signaling. We show that upon DNA damage, NM1 forms a complex with p53 and activates the expression of checkpoint regulator p21 (Cdkn1A) by PCAF and Set1 recruitment to its promoter for histone H3 acetylation and methylation. We propose a role for NM1 in the transcriptional response to DNA damage response and maintenance of genome stability.

Department of Biology of the Cell Nucleus Institute of Molecular Genetics AS CR v v i Videnska 1083 142 20 Prague Czech Republic

Department of Molecular Biosciences The Wenner Gren Institute Stockholm University SE 106 91 Stockholm Sweden

Laboratory of Epigenetics of the Cell Nucleus Institute of Molecular Genetics of the ASCR Division BIOCEV Prague Czech Republic

Science Division Biology Program New York University Abu Dhabi P O Box 129188 Abu Dhabi UAE

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