端粒DNA序列高度重复，复制较为困难，通常需要额外的蛋白因子进行辅助。CST蛋白能够激活受阻复制叉、重启受阻端粒复制。然而其并不具备起始DNA复制所必需的酶活性，重启复制的机制尚未明确。我们发现解旋酶RECQ4可以与CST发生相互作用，同时解旋高级结构并与MCM10协同作用起始DNA合成，我们的结果还进一步证实其敲除能够导致端粒复制叉的停滞并引发复制性损伤。据此我们提出以下论点，“端粒复制受阻时，CST与所产生的单链端粒DNA相互结合，随后RECQ4通过与CST的相互作用结合到受阻复制叉，并与MCM10一起在相邻的休眠复制起始位点，共同组装复制前体，重启受阻复制位点”。本课题中我们将系统的研究RECQ4重启端粒受阻复制叉的具体机制，该研究将开拓对RECQ4端粒功能的探索，并为进一步明确端粒DNA复制的分子机制奠定基础，同时为以调控端粒复制为手段的肿瘤或衰老治疗提供方案。

Telomere DNA with reparative guanine-rich sequence were thought to be a physical blockade of the end chromosomes. DNA replication in telomere area is deemed to be difficult compared with the other parts of genome, which requires additional co-factors to facilitate the process. In the previous study, we have reported that the newly identified telomere binding protein complex CTC1-STN1-TEN1 could reinitiate the stalled telomere replication forks, through firing the dominate origins nearby. However, CST complex could only bind to the ssDNA and doesn't exhibit the properties of DNA polymerase, topoisomerase or helicase, which is required for the DNA replication re-initiation, suggesting there must be some other replication factors participating in the process. To further investigate the mechanism of replication re-initiation in telomere, we managed to identify the proteins which could interact with CST, and RECQ4 turns out to be one of these co-factors. RECQ4 is a member of RECQ helicase family, which could unwind double strand DNA and initiate the replication. Mutations in RECQ4 lead to specific features of Rothmans-Thomson syndrome, including spares hair, skeletal abnormalities, short life span and increased risk of cancer. Moreover, we identified that RECQ4 knockout could induce telomere replication disorders as well as stalled telomere replication forks. Based on these observations, we raised our proposal, that is "When replication fork stalling occurs, CST could locate to these regions via its ssDNA binding domain, subsequently RECQ4 could be recruited to the stalled forks through the interaction with CST, then initiates the Pre-initiation complex formation and restarts the stalled replication". We are going to further investigate the mechanism of RECQ4 in restarting the stalled replication fork restart here, it will not only broad our knowledge of telomere function of RECQ4 but also guide our current aging and cancer therapy which based on regulating telomere replication.