A team led by Academician Tao-shih Hsieh, Distinguished Research Fellow and Director at the Institute of Cellular and Organismic Biology, recently discovered that a new gene Wuho plays a critical role in the maintenance of genome stability. This study was published in the journal PLOS Biology on January 11, 2016.
　　Accurate genome replication is essential for the transmission of genetic information, and this process is vulnerable to factors that can induce DNA damage or block replication. To avoid this and achieve genome stability, many enzymes need to coordinate their activities at the replication forks (the area where the two DNA strands separate to replicate), thereby ensuring high efficiency and fidelity. Replication occurs simultaneously in both strands, but DNA polymerases only work in one direction (5’-to-3’), and while synthesis of one strand proceeds continuously, synthesis of the other must occur via small DNA fragments that need to be joined together after the removal of their 5’ ends by the flap endonuclease 1 (FEN1). In addition, FEN1 has a gap endonuclease activity that can potentially introduce strand breaks at the sites of replication. This article addresses the mechanistic basis of the genome protection function of Wuho. Wuho’s genome guardian function is through the interaction with FEN1 at the replication fork to promote its flap endonuclease activity but dampen the gap endonuclease activity. The consequence of Wuho’s regulation on FEN1 enables it to reduce the potential risk of DNA damage introduced by FEN1 during replication. These results suggest a critical role of Wuho in protecting the integrity of replication forks.
　　Wuho’s research is a team work across different disciplines. Besides Academician Hsieh’s team, members also include Dr. Peilin Chen at the Research Center for Applied Sciences and Dr. Fan-Ching Chien at the Department of Optics and Photonics of National Central University. This project was supported by Academia Sinica (AS-103-TP-B02, The dynamics and localization of DNA Replication and Repair Nano-machine)
　　The full article entitled “Wuho Is a New Member in Maintaining Genome Stability through its Interaction with Flap Endonuclease 1” can be found online on the PLOS Biology website at: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002349