2013-01-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/698037摘要：為了維持DNA的完整性，避免在細胞分裂時將錯誤的核&#33527;酸遺傳給下一代子細胞，真核細胞發展出了縝密的偵測與修補系統，防止正常細胞DNA突變至難以收拾，嚴重的話甚至會啟動細胞凋亡機制來預防不正常細胞有進一步癌化的可能。因此當DNA受到紫外光、輻射線或化療藥物傷害時，會啟動偵測系統，活化蛋白質磷酸&#37238;對下游受質進行磷酸化作用，藉以停止或延長細胞週期運轉來等待DNA被修復或直接活化細胞凋亡機制。利用系統生物學的方法，我們將研究在DNA受到傷害前和受到傷害後細胞內蛋白質轉譯後修飾的變化、DNA結合蛋白的變化以及轉錄體的變化，目的在找到新的DNA傷害發生時的生物標記，藉由這些生物標記的產生預測細胞DNA傷害發生後的命運，希望能進一步了解調控DNA傷害反應的機制。<br> Abstract: Maintenance of genomic integrity and protection against harmful mutagenic effects of DNA damage rely on DNA damage response machinery, a complex network of signalling and effector pathways that coordinate cell cycle checkpoints with DNA repair and cell death mechanisms. In response to DNA lesions, sensor proteins, such as PARP-1/Mre11-Rad50-Nbs1/Rad9-Rad1-Hus1, activate the signal transducing kinases, ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) to phosphorylate downstream checkpoint effectors, such as Cdc25/p53/E2F, to regulate cellular responses and ensure error-free DNA replication. In this proposal, we would like to use the systems biology to study the differences before and after DNA damage, including novel post-translational modifications, chromatin-bound proteins, and transcriptome analysis. This approach is aimed to find new biomarkers involved in DNA damage response. These results will reveal further highlights on DNA damage response.DNA傷害磷酸激&#37238轉譯後修飾DNA結合 蛋白轉錄體生物標記DNA damagekinasepost-translational modificationchromatin-bound proteinstranscriptomebiomarker