Nitrogen mustard induces dynamic nuclear protein spectrum change and DNA-protein crosslinking, with p97 mediating repair

• DOI: 10.1016/j.heliyon.2024.e37401
• Publication Date: 2024-09-04T06:54:11Z
• Authors: Jin Cheng; Haoyin Liu; Wenpei Yu; Xunhu Dong; Yan Sai; Feng Ye; Guorong Dan; Mingliang Chen; Yuanpeng Zhao; Xi Zhang; Zhongmin Zou
• Keywords: MG132; Protein Degradation; Nuclear export signal

Nitrogen mustard (NM) is a chemotherapeutic agent capable of alkylating nucleophilic proteins and DNA, causing severe cell damage. However, no reports have been on the dynamic changes in proteomics induced by NM. In this study, we established model acute exposure to NM for 1 h continuous cultured 24 after removal (repair stage) using 16HBE cells. The nuclear protein spectrum crosslinked with DNA were analyzed, function p97 during damage was examined. An hour resulted into nucleus, which mainly involved acid-related issues. After h, return normal process types amounts differentially expressed inhibited si-p97. main processes si-p97 intervention nucleocytoplasmic transport, processing endoplasmic reticulum, metabolic abnormalities, DNA-response; however. increased DNA-protein crosslinking (DPC), total-H2AX, p-H2AX. contrast, only further or maintained their levels at yet not h. effect proteasome inhibitor, MG132, similar that siRNA DVC1, partner p97, also DPC content. Both si-DVC1 cytoplasmic (PSMD2). These results suggest induces spectral changes, rapid influx formation, double-strand breaks. Furthermore, our data indicated maintenance withdrawal, requiring participation DVC1 proteasome.