染色質重塑蛋白(Chromatin remodeling complex)可以透過水解ATP催化核小體 的滑動(Sliding)及移除(Eviction)，具有改變染色質結構的功能，在轉錄、複製及 DNA修復中都扮演重要的角色。
在先前研究中發現染色質重塑蛋白SMARCA5能夠改變核小體間距、促進染色 質重組和壓縮(Compaction)，以及在DSB產生時幫助募集HR相關蛋白BRCA1進行 DNA雙股斷裂修復。然而目前SMARCA5在複製壓力下對於複製叉的功能並不清楚， 因此本篇研究著重探討SMARCA5在遭遇複製壓力時對細胞的影響為何。我們的結 果顯示SMARCA5表現降低會導致SCE發生次數增加，表示當SMARCA5表現降 低後，會導致複製叉在遭遇複製壓力時無法有效進行損傷修復，最終造成DSB以及 SCE的提升。除此之外，利用DNA fiber的實驗，我們發現SMARCA5表現降低會 導致IdU/CldU的比值降低，代表複製叉的保護機制異常，表示SMARCA5可能具 有複製叉保護的功能或是能夠幫助募集複製叉保護蛋白。結論，在複製壓力下 SMARCA5能夠促進DNA損傷修復及促進複製叉的保護機制。

Chromatin remodeling complexes catalyze nucleosome loading, sliding, and eviction through ATP hydrolysis. Since chromatin remodeling complexes can change chromatin structure, they play important roles in transcription, DNA replication, and repair. In recent studies, it was found that the chromatin remodeling protein SMARCA5 can change the distance between nucleosomes, promote chromatin recombination and compaction. During DSB repair, SMARCA5 can promote the HR-related protein BRCA1 recruitment. However, the mechanisms of SMARCA5 for DNA replication under replication stress is still not clear. Therefore, our study focuses on the function of SMARCA5 when replication fork encounter replication stress. Our results reveal that the SMARCA5-depleted cells lead to an increased frequencies of sister chromatid exchange (SCE), indicating that SMARCA5 could prevent stalled forks from collapse when encountering replication stress. The increasing frequency of collapsed forks will be ultimately repaired by homologous recombination, lead to SCE. In addition, SMARCA5-depleted cells show degradation of nascent DNA by the DNA fiber assay, indicating that SMARCA5 may take part in fork protection during replication stress. Taking together, our results reveal that SMARCA5 is able to protect stalled forks from collapse to maintain genome stability during replication stress.

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