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.

核肌球蛋白1（NM1）与关键的核功能有关。与肌动蛋白一起，已经证明它可以启动和调节转录，它是染色质重塑复合体B-WICH的一部分，并负责响应外部刺激而对染色体区域进行重排。在这里，我们表明删除小鼠胚胎成纤维细胞中的NM1会导致染色质和转录失调，从而影响DNA损伤和细胞周期基因的表达。NM1 KO细胞表现出增加的DNA损伤和细胞周期进程，增殖和凋亡的变化，与p53信号转导受损的表型相容。我们显示出DNA受损后，NM1与p53形成复合物并激活检查点调节剂p21（Cdkn1A），通过PCAF和Set1募集到其启动子，以进行组蛋白H3乙酰化和甲基化。我们提出NM1在对DNA损伤反应和维持基因组稳定性的转录反应中的作用。