2007-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/652208摘要：研究顯示人類p29蛋白屬於可與染色質結合的蛋白質，並可與MCM3蛋白質作用，細胞若轉殖p29的短鏈 siRNA會造成進行DNA複製的細胞減少，同時p21和p107的表現量會增加，MCM3和DNA polymearase  的表現量會減少；進一步利用紫外光照射已轉殖p29短鏈 siRNA的細胞，結果會增加更多停留在G1時期的細胞數目，Chk1的表現量與磷酸化均會降低，推測缺少p29蛋白的細胞無法完成DNA複製前的先期準備工作，因而影響細胞週期的進行；最新的研究發現p29可能與遺傳疾病 Fanconi anemia有關。 為了進一步瞭解p29的生理功能，我們提出三年計畫，包含了解轉殖p29短鏈 siRNA如何影響p21, p107, Chk1和FANCD2的表現；p29與FANCG的作用機制和參與在缺乏FANCG和FANCD2表現的細胞在DNA受傷害時的效應分析；我們與國家動物中心合作已建立mp29基因轉殖鼠，我們將分析mp29過量表現的小鼠在受到 DNA損傷時對生物體的影響。 <br> Abstract: Human p29 has been demonstrated to associate with GCIP, a cyclin D-interacting protein, in the yeast two-hybrid method and in vitro GST pull-down assay. We developed anti-p29 monoclonal antibody and immunofluorescence staining showed a dynamic distribution of p29 in mitosis, abundantly in the nucleus during G1 and G2 phases. We found that p29 is a chromatin-associated protein and p29 could interact and co-localize with MCM3. The silencing of p29 expression using siRNA approach induced an increased population in G1 phase in response to DNA damage treatment. These findings provide evidence that the function of p29 may be related to cell cycle progression in G1 phase. Recent studies showed that p29 could interact with FANCG and silencing of p29 could suppress the expression of FANCD2. Therefore, we are proposing a three-year project to delineate the function of p29, including to investigate how silencing of p29 regulated the expression of p21, p107, Chk1, and FANCD2; to examine the interaction between p29 and FANCG and to test whether p29 can complement the defects in FANCD2 or FANCG mutant cells in response to DNA damage treatments; and to determine the developmental defects of mp29 transgenic mice and its responses to DNA damage.p29mp29FANCGp107基因轉殖p29mp29FANCGp107transgene