细胞进化出一整套保守的分子机制去应对内源及外源的导致DNA损伤的威胁,保护遗传信息的稳定。这些机制包括感知、传递DNA损伤信号及修复DNA损伤等，统称为DNA损伤响应（DDR）。DDR是一个复杂的分子网络，整个过程受诸多的蛋白质翻译后修饰，包括磷酸化、泛素化、乙酰化等严格控制。相比于这些研究较多的翻译后修饰，赖氨酸巴豆酰化修饰(KCr)发现的较晚，且其是否参与到DDR调控过程中完全未知。我们用定量质谱分析DNA损伤前后细胞总体KCr修饰的动态变化，发现了大量响应DNA损伤的KCr位点，其中部分得到了Western blot证实，并初步研究了调控机制。用巴豆酸盐处理细胞增加整体的KCr水平会抑制DNA修复效率并阻止重要的DDR因子到损伤位点的募集。这些前期结果说明KCr参与了DDR调控，我们计划对此开展深入研究，初步揭示KCr受DNA损伤调控及影响DDR的分子机制。

To cope with endogenous and exogenous insults that cause DNA damage, cells evoke conserved pathways that encompass the sensing, signalling and repair of damaged DNA, collectively termed the DNA damage response (DDR) to safeguard their genetic information. The DDR is an intricate molecular network which is tightly controlled by the protein post-translational modifications (PTM) including phosphorylation, ubiquitylation, acetylation and others. Compared to those well-studied PTMs, the lysine crotonylation (KCr) was observed late. It is still unclear that whether this kind of modification involves in DDR or has an impact on DDR. In this study, we used mass spectrometry-based proteomics to quantify dynamic changes of the whole KCr of human cell lines before and after DNA damage. We found that levels of KCr on multiple sites can be altered upon DNA damage. Some of them were proved by western blot and the regulatory mechanisms were uncovered. Increasing KCr levels by crotonate addition suppress DSB repair efficiency and block the recruitment of well-known DDR factors to damage sites. KCr may also be employed by DDR. We thus aim to further establish the functional link between some KCr and DDR and to reveal detail mechanisms by which DNA damage regulate KCr levels and cells use KCr to influence DDR.