细胞增殖是器官发育的必要条件，而DNA顺利完成复制是细胞增殖的前提。DNA复制时必然会经过基因转录活跃区，这时复制和转录彼此间就会互相干扰。在真核细胞增殖期间，rRNA基因属于高转录基因，加之rRNA基因串联重复形成基因簇，因此在器官发育时rDNA区域的DNA复制必须克服与rRNA转录之间的矛盾，但目前尚不清楚有哪些核仁因子参与协调该过程。Bms1是一个核仁蛋白，我们之前报道过斑马鱼Bms1l失活导致小肝脏表型、Bms1与Rcl1形成复合体参与18S rRNA的加工成熟。我们最近意外发现bms1l 突变体中DNA复制发生异常、核仁数目增加、复制相关蛋白p53及RPA2等的表达显著上调并富集于核仁中。据此我们推测Bms1l不仅参与18S rRNA加工成熟，还可能在细胞增殖期间在调和rDNA复制与rRNA转录之间的矛盾中发挥重要功能。本研究旨在阐明Bms1l的新功能以揭示肝脏发育调控的新机制。

Cell proliferation is one of the basic cellular activities during organ development. DNA replication is the prerequisite for cell proliferation. During DNA replication, replication forks will inevitably encounter the ongoing gene transcription on the same template. In this case, there will be a physical conflict between DNA replication and gene transcription. In high eukaryotes, rRNA genes are tandemly repeated in the genome to form a gene cluster (rDNA region). rRNA is highly transcribed even during DNA replication. Therefore, with the conflict between DNA replication and gene transcription a prominent feature in the rDNA region especially during organogenesis, organisms must have developed a mechanism to circumvent this clash. However, we have limited knowledge regarding the nucleolar factors involved in this process. Bms1 is a nucleolar protein. Our previous studies have shown that loss-of-function of the zebrafish Bms1l led to a small liver phenotype and that Bms1l and Rcl1 form a complex that is essential for the processing and maturation of 18S rRNA. Recently, we surprisingly found that the bms1l-/- mutant displayed abnormal DNA replication and increased number of nucleoli. We also found that p53 and its downstream genes were significantly up-regulated and proteins related to DNA replication fork progression (e.g RPA2 and Rad51) were drastically up-regulated in the bms1l-/- mutant. Moreover, p53 and RPA2 are enriched in the nucleolus in the bms1l-/- mutant. Based on these data, we propose that Bms1l, in addition to its role in 18S rRNA processing and maturation, serves as a regulator of DNA replication by resolving the conflict between replication and transcription. The proposed research plan will try to unravel the possible role(s) of Bms1l in DNA replication, with specific focus on studying the role of Bms1l in the formation of the replication fork barrier (RFB) within the rDNA gene cluster. This will allow us to understand the molecular mechanism of Bsm1l in promoting liver development. So far, there is no report on the function of Bms1 in DNA replication. The outcome of our research will extend our understanding of the biological function of Bms1 in organogenesis.