科研领域描述
本实验室主要兴趣在于：
真核细胞DNA复制机理。
真核细胞生长分裂及checkpoint调控机理。
DNA复制是细胞生长分裂过程中的一个最基本生化反应。 其特点是高度的准确性及严格的调控， 以保证子细胞能从母细胞里得到一套完整的染色体DNA。 我们的研究专注于真核细胞DNA复制起始的机理及调控。 最近， 我们发现并证明Sap1是DNA复制起始反应所必需的蛋白。 现正对其功能及相互作用蛋白进行深入研究。 我们也研究DNA复制叉里的生化反应。
Checkpoin调控细胞生长分裂。 其根本目的是维护细胞内染色体DNA完整。 DNA复制叉的停顿或DNA损伤激活Checkpoint, 但其机理不清楚。 用生化及遗传的方法，期望能发现一些新的Checkpoint激活分子。 我们现正研究Fen1及其它一些蛋白在Checkpoint中的作用。
Research Description:
Our studies try to elucidate, at molecular level, the mechanisms of initiation of eukaryotic chromosomal DNA replication and checkpoint control.
DNA replication is a fundamental biochemical reaction during cell division cycle. It is highly complicated and sophisticatedly regulated to guarantee each daughter cell gets a complete copy of chromosomal DNA from its mother cell. Our research focuses on the initiation and regulation of chromosomal DNA replication in the fission yeast S. pombe and human cells. Recently, we found and demonstrated that S. pombe Sap1 is an essential replication initiation protein. It is found that Sap1 is required to load the initiation protein Cdc18 to chromatin for the assembly of pre-replication complex. Currently, we are investigating what proteins interact with Sap1 and whether human cells have a Sap1-like protein. We are also interested in the reaction that occurs in replication fork.
Checkpoint control regulates cell growth cycle and it is essential to maintain genomic integrity. A major question in checkpoint control is how the pausing of DNA replication fork or DNA damage activates checkpoint. With approaches of biochemistry and genetics, we study what proteins are involved in checkpoint activation. Currently, we are examining the roles of Fen1, PCNA, and some other proteins in stabilizing replication fork and checkpoint activation.
代表性论文
1. Daochun Kong, Thomas R. Coleman & Melvin L. DePamphilis , Xenopus origin recognition complex (ORC) initiates DNA replication preferentially at sequences targeted by Schizosaccharomyces pombe ORC. , EMBO J. , 2003 , 22:3441-3450.
2. Daochun Kong and Melvin DePamphilis , Site specific ORC binding, pre-replication complex assembly, and DNA synthesis at S. pombe replication origins. , EMB0 J. , 2002 , 21: 5567-5576
3. Daochun Kong & Melvin L. DePamphilis , Site-specific DNA binding of the Schizosaccharomyces pombe origin recognition complex is determined by the Orc4 subunit , MCB , 2001 , 21: 8095-8103.
4. K-Y. Moon, Daochun Kong, J-K Lee, S. Raychandhuri, and Jerard Hurwitz. , Identification and reconstitution of the origin recognition complex from Schizosaccharomyces pombe. , Proc. Natl. Acad. Sci. USA , 1999 , 96: 12367-12372.
5. Daochun Kong, Jack D. Griffith, and Charles C. Richardson , T7 gene 4 helicase promotes branch migration through non-homologous, mismatched, or ultraviolet-irradiated DNA regions , Proc. Natl. Acad. Sci. USA , 1997 , 94: 2987-2992
6. Daochun Kong and Charles C. Richardson , Single-stranded DNA binding protein and DNA helicase of bacteriophage T7 mediate homologous DNA strand exchange , EMBO J. , 1996 , 15: 2010-2019.
|
