DNA Recombination and Repair

DNA Recombination and Repair

Genomic DNA is maintained with high fidelity to guarantee the integrity of genetic information. Damaged DNA must be properly repaired by sophisticated DNA repair systems to sustain cell viability and genomic stability. Homologous recombination is the major pathway for repairing DNA double strand breaks and for re-initiating stalled replication forks in E. coli and eukaryotes. In E. coli, there are several important proteins involved in homologous recombination: RecA protein is essential for pairing homologous DNA, and for promoting the strand exchange process. RecBCD protein is a DNA helicase/nuclease that processes damaged DNA ends and generates ssDNA.

Homologous recombination has been thought to be the potential pathway for targeting gene delivery. Defects in human helicase family genes have implications in cancer and aging process. Human Rad51, the structural and functional homolog of RecA, has been found to directly interact with breast cancer genes. We are interested in understanding the molecular mechanisms of the proteins involved in this pathway through the combination of the conventional biochemistry study and the single-molecule biophysics approaches.

DNA重組與修復

基因體DNA必須要維持其完整性，以確保其攜帶的基因資訊在每個代間，完整的傳遞下去不受破壞。然而，DNA常常受破壞，受損DNA必須要經由一套成熟的修復機制妥善修復，以維持細胞存活與基因體的穩定性。同源重組是一個主要修復DNA雙股斷裂，以及在大腸桿菌等真核系統中重啟停滯DNA複製反應的重要機制。在大腸桿菌中，同源重組牽涉到幾個重要的蛋白：RecA蛋白，主要功用在配對同源的DNA序列，並促進股交換反應之發生；RecBCD蛋白，是具有解旋酶以及核酸酶的活性，作用於受損的DNA尾端，並製造單股DNA。

同源重組反應被視為一個潛在的基因療法輸送機制。有跡象顯示，當人類解旋酶反應受損時會造成癌症以及老化。人類Rad51蛋白（在結構與功能上被視為RecA蛋白的同源體），已經被發現與乳癌有直接相關。因此，我們團隊結合了傳統生化實驗技術以及單分子生物物理的方法，致力於了解同源重組反應之機制。