DNA複製壓力對基因組的完整性構成了巨大威脅。 其中，DNA轉位酶SMARCAL1和HLTF被募集到停滯的複製叉中，去穩定並防止複製叉的斷裂。HLTF和SMARCAL1是否具有功能上的重疊性或它們是否參與解決不同類型的DNA損傷，這其中的機制並不清楚。在本篇研究中，我們發現SMARCAL1在複製叉穩定性中扮演重要的角色。 在 Sister chromatid exchange (SCE) 的實驗中發現，SMARCAL1的缺失提高了姐妹染色體互換。在單分子DNA Fibre分析顯示，在MMS的處理造成DNA損傷下，SMARCAL1會降低DNA複製的速率。另外，在SMARCAL1和HLTF雙缺失下更明顯的提高了細胞對藥物Methyl methanesulfonate (MMS)的敏感性。此外，SMARCAL1/HLTF雙缺失下導致RPA32 S4 / S8兩個位點的磷酸化，代表複製叉的斷裂。我們發現在DNA複製壓力下，SMARCAL1和HLTF對維持複製叉的穩定性是具有協同的作用。

DNA replication stress imposes a great threat to the integrity of genome. SMARCAL1 and HLTF DNA translocases are recruited to stalled replication forks to promote fork reversal; therefore, stabilizing forks and preventing the collapse of replication forks. However, whether HLTF and SMARCAL1 function redundantly or they are involved in resolving different type of DNA lesions remains unclear. Here we report that SMARCAL1 plays an important role in fork stability. The depletion of SMARCAL1 generates high frequency of sister chromatid exchanges (SCEs). Strikingly, the single molecule DNA fibre analysis revealed that SMARCAL1 contributes to the slowing of replication progression in response to MMS-induced DNA lesions. The combined depletion of SMARCAL1 and HLTF causes more sensitivity to DNA damaging agent, methyl methanesulfonate (MMS), than the single depletion of each gene. Furthermore, SMARCAL1/HLTF double-depleted cells results in the hyperphosphorylation of RPA32 at S4/S8 sites, indicating the collapse of forks. Our findings reveal that SMARCAL1 and HLTF have additive effects on the maintenance of fork stability during replication stress.

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