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  • 學位論文

Cohesion Associated Regions特徵之生物資訊方法研究

Bioinformatic Study on Characteristics of Cohesion Associated Regions

指導教授 : 曹承礎
共同指導教授 : 高明達(Ming-Tat Ko)

摘要


細胞分裂是一個很重要的生命現象,在細胞分裂的過程中,為了確保染色體能正確的複製和分離,cohesion在S phase連結姊妹染色體,一直到anaphase才消失。最近,控制cohesion的蛋白質逐漸被發現。然而,關於cohesion associated regions(CARs)的特徵卻了解不多,而且絕多數的觀察是來自於單一的CAR,而非在多數的CARs發現。 本研究利用生物資訊的方法來辨識CARs的特徵。我們透過文獻找出一些可能和CAR相關的因素,包括the intergenic regions of WC orientation, scaffold/matrix attachment regions (S/MARs), autonomously replicating sequences (ARS), palindrome, tRNA genes, yeast retrotransposons and nearby long terminal repeats (LTRs)。再利用我們提出的衡量距離方法和機率模型來探討這些因素和CARs的關聯性。 我們發現在百分之九十五的信心水準下,the intergenic regions of WC orientation, scaffold/matrix attachment regions (S/MARs), autonomously replicating sequences (ARS), palindrome和tRNA genes並不是隨機在CARs附近出現。也就是說,這些因素的確和CARs有關聯。

並列摘要


Mitosis is a very important phenomenon of life. In the mitosis of cells, cohesion connects the newly duplicated chromosomes (sister chromatids) from the S phase to anaphase to ensure the correct splitting and distribution of the genome. Recently, many proteins that control cohesion have been discovered. However, most knowledge about the characteristics of cohesion associated regions (CARs) has been gained from experiments on individual CARs. This study seeks to identify the characteristics of CARs by means of a computational approach. We review the literature and obtain a list of potential factors that may associate with CARs, including the intergenic regions of WC orientation, scaffold/matrix attachment regions (S/MARs), autonomously replicating sequences (ARS), palindrome, tRNA genes, yeast retrotransposons and nearby long terminal repeats (LTRs). We define a distance measure and propose a probabilistic model to investigate the association of each potential factor with CARs. We find that the intergenic regions of WC orientation, palindromes, S/MARs, tRNA genes and ARS do not randomly colocalize with CARs under the 95% confidence level.

參考文獻


1. (Nasmyth,2002) K. Nasmyth. 2002. Segregating sister genomes: the molecular biology of chromosome separation. Science. 297:559-565.
2. (Uhlmann, 2003) F. Uhlmann. 2003. Separase regulation during mitosis. Biochem Soc Symp. 70:243-251.
3. (Guacci et al., 1997) V. Guacci, D. Koshland, and A. Strunnikov. 1997. A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae. Cell. 91:47–57.
4. (Megee et al., 1999) P.C. Megee, C. Mistrot, V. Guacci, and D. Koshland. 1999b. The centromeric sister chromatid cohesion site directs Mcd1p binding to adjacent sequences. Mol. Cell. 4:445–450.
5. (Blat and Kleckner, 1999) Y. Blat, and N. Kleckner. 1999. Cohesins bind to preferential sites along yeast chromosome III, with differential regulation along arms versus the centric region. Cell. 98:249–259.

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