探討Rap1蛋白質磷酸化在端粒的功能

Investigating the Functions of Phosphorylated Rap1 on Telomere Regulation

張正妍(Cheng-Yen Chang)

指導教授 ： 鄧述諄

國立臺灣大學/醫學院/微生物學研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.11169

摘要

端粒是維持染色體末端穩定性重要的構造，在酵母菌中，Rap1為一DNA結合蛋白，能和有結合關係的蛋白質一起作用去保護端粒，防止染色體末端和另外一條染色體末端因為修復的關係而不正常的連結在一起(NHEJ)，並且保護端粒不會受到由端粒酶調控所引起不正常端粒延長的現象。在本篇研究中我們發現，在端粒縮短及DNA雙股斷裂下能引起Rap1蛋白質中絲胺酸731位點上發生磷酸化的現象，並且這個磷酸化是透過Mec1/Tel1所控制。我們也發現Rap1的磷酸化能保護端粒，防止端粒和端粒之間以直接黏接的方式形成連結的結構。除此之外，我們發現Rap1的磷酸化能夠促使Rap1和Rif2蛋白質停留在端粒上。總結以上，我們的發現暗示Rap1蛋白質的磷酸化對於端粒的調控是重要的。

關鍵字

Rap1 ； 磷酸化 ； NHEJ ； 端粒調控 ； Rif2 ； Mec1 ； Tel1

並列摘要

Telomere maintenance is required for chromosome stability. In yeast Saccharomyces cerevisiae, the telomeres double strands binder, Rap1, together with interaction proteins protects telomeres from end-to-end fusion and telomere-mediated elongation. In this study, we found that under telomere shortening and double strand breaks, Rap1 serine 731 could be phosphorylated by Mec1/Tel1 check point kinases. Importantly, Rap1 phosphorylation could protect telomeres from non-homologous end join (NHEJ). Moreover, the phosphorylation could enhance Rap1 and Rif2 proteins binding on telomeres. All together, these results suggest that phosphorylation on Rap1 serves as an essential post-translational modification mark on telomere regulation.

並列關鍵字

Rap1 ； Phosphorylation ； NHEJ ； Telomere regulation ； Rif2 ； Mec1 ； Tel1

參考文獻

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