微生物的DNA复制调控研究一直是当代生命科学最受关注的前沿领域之一。近日,华中农业大学生命科学技术学院教授何正国带领的课题组在DNA复制和细胞周期调控研究领域取得重要进展。
研究人员发现了古菌的DNA复制起始蛋白和DNA聚合酶之间存在物理和功能性的相互作用,并首次在古菌生命体中阐明了DNA复制起始和延伸两个过程之间的分子偶联机制。该项成果发表在国际学术期刊美国《国家科学院院刊》(PNAS)上。
据介绍,DNA等遗传物质的精确复制是生命现象最本质的内容。DNA复制及细胞周期调控的紊乱将直接导致人的癌症、衰老等重要疾病的发生。然而,由于人和高等真核生物的这些遗传调控机制相当复杂,目前主要以微生物为模式材料开展相关的分子机制研究。
古菌是一种常常生活在极端环境,如高温、高盐、极端pH等条件下的特殊生命形式,有趣的是在这类特殊生物中发现含有人和高等真核生物的DNA复制调控关键酶,因而成为重要的模式材料。
近几年,国外科学家纷纷转入利用这种特别的古菌作为研究材料,期望加快疾病机制的研究,促进关键调控基因以及新药靶的发现。
何正国课题组经过长期研究发现,古菌的DNA复制起始蛋白和DNA聚合酶在体内和体外都能发生物理相互作用,同时这些复制起始蛋白还能双重调控DNA聚合酶的核心复制功能,这些发现首次在古菌生命体中建立了DNA复制起始和延伸两个关键过程之间的分子偶联机制。鉴于相关的分子细节在高等真核生物中仍然没有被阐明,因此该发现为最终揭示高等生物的复杂机制提供重要线索。(生物谷Bioon.com)
生物谷推荐原始出处:
PNAS May 12, 2009 vol. 106 no. 19 7792-7797
Archaeal eukaryote-like Orc1/Cdc6 initiators physically interact with DNA polymerase B1 and regulate its functions
Lu Zhang,1, Lei Zhang,1, Yi Liu,1, Shifan Yang, Chunhui Gao, Hongchao Gong, Ying Feng and Zheng-Guo He,2
National Key Laboratory of Agricultural Microbiology, Center for Proteomics Research, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
Archaeal DNA replication machinery represents a core version of that found in eukaryotes. However, the proteins essential for the coordination of origin selection and the functioning of DNA polymerase have not yet been characterized in archaea, and they are still being investigated in eukaryotes. In the current study, the Orc1/Cdc6 (SsoCdc6) proteins from the crenarchaeon Sulfolobus solfataricus were found to physically interact with its DNA polymerase B1 (SsoPolB1). These SsoCdc6 proteins stimulated the DNA-binding ability of SsoPolB1 and differentially regulated both its polymerase and nuclease activities. Furthermore, the proteins also mutually regulated their interactions with SsoPolB1. In addition, SsoPolB1c467, a nuclease domain-deleted mutant of SsoPolB1 defective in DNA binding, retains the ability to physically interact with SsoCdc6 proteins. Its DNA polymerase activity could be stimulated by these proteins. We report on a linkage between the initiator protein Orc1/Cdc6 and DNA polymerase in the archaeon. Our present and previous findings indicate that archaeal Orc1/Cdc6 proteins could potentially play critical roles in the coordination of origin selection and cell-cycle control of replication.