三核苷酸重複序列擴增

三核苷酸重複序列擴增（英語：Trinucleotide repeat expansion, Triplet repeat expansion），也稱三核酸重複序列擴增、三核苷酸重複擴增、三核苷酸擴增等，是一種可能導致三核苷酸重複序列疾病（英語：trinucleotide repeat disorder）的DNA 突變。在動態遺傳學（英語：dynamical genetics）中被稱為動態突變（英語：dynamic mutation）。^[1]

在DNA複製中，三核苷酸重複序列擴增由DNA複製時的滑動現象（英語：slippage）^{[註 1]}造成^[2]。DNA序列在不少區域都有重複序列，使得母鏈和子鏈鹼基互補配對有時會產生環狀結構。如果環狀結構發生於子鏈則DNA複製後重複序列的重複次數會增加，發生於母鏈則重複次數減少，重複次數增加的概率被認為大於減少的概率。而重複序列擴增的規模越大，越有可能導致疾病，其導致的疾病也越嚴重。DNA和RNA的互動也可能參與了三核苷酸重複序列擴增這一導致序列不穩定的現象中。^[3]

DNA修復也會導致三核苷酸重複序列擴增。^[4]三核苷酸重複序列損傷（英語：DNA damage (naturally occurring)）時，會引發同源重組、非同源性末端接合、錯配修復、鹼基切除修復等修復機制來修復損傷的DNA。這些過程中，錯配鹼基切除後往往需要同DNA複製一般重新配對，因而有概率產生三核苷酸重複序列擴增^[4]。

三核苷酸重複序列的重複次數與亨丁頓舞蹈症等一眾三核苷酸重複序列疾病的病程、危重程度、發病年齡正相關。^[5]^[4]

參見

遺傳早現
三核苷酸重複序列疾病（英語：trinucleotide repeat disorder）

注釋

^ 有時也稱「拷貝選擇」複製（英語：Copy choice duplication）

參考資料

^ Richards RI, Sutherland GR. Dynamic mutation: possible mechanisms and significance in human disease. Trends Biochem. Sci. 1997, 22 (11): 432–6. PMID 9397685. doi:10.1016/S0968-0004(97)01108-0.
^ Salinas-Rios V, Belotserkovskii BP, Hanawalt PC. DNA slip-outs cause RNA polymerase II arrest in vitro: potential implications for genetic instability. Nucleic Acids Res. 2011, 39 (15): 1–11. PMC 3177194 . PMID 21666257. doi:10.1093/nar/gkr429.
^ McIvor EI, Polak U, Napierala M. New insights into repeat instability: Role of RNA•DNA hybrids. RNA Biol. 2010, 7 (5): 551–8. PMC 3073251 . PMID 20729633. doi:10.4161/rna.7.5.12745.
^ ^4.0 ^4.1 ^4.2 Usdin K, House NC, Freudenreich CH. Repeat instability during DNA repair: Insights from model systems. Crit. Rev. Biochem. Mol. Biol. 2015, 50 (2): 142–67. PMC 4454471 . PMID 25608779. doi:10.3109/10409238.2014.999192.
^ News Release, Weizmann Institute of Science, "Scientists at the Weizmann Institute, using computer simulations, have provided an explanation as to why certain genetic diseases caused by repeats in the code are 「genetic time-bombs」 whose onset and progression can be accurately predicted," November 21, 2007, at http://80.70.129.162/site/en/weizman.asp?pi=371&doc_id=5042 （頁面存檔備份，存於網際網路檔案館）. Retrieved on 2007-12-30.

[2] 有時也稱「拷貝選擇」複製（英語：Copy choice duplication）

[pmid9397685-1] Richards RI, Sutherland GR. Dynamic mutation: possible mechanisms and significance in human disease. Trends Biochem. Sci. 1997, 22 (11): 432–6. PMID 9397685. doi:10.1016/S0968-0004(97)01108-0.

[pmid21666257-3] Salinas-Rios V, Belotserkovskii BP, Hanawalt PC. DNA slip-outs cause RNA polymerase II arrest in vitro: potential implications for genetic instability. Nucleic Acids Res. 2011, 39 (15): 1–11. PMC 3177194 . PMID 21666257. doi:10.1093/nar/gkr429.

[pmid20729633-4] McIvor EI, Polak U, Napierala M. New insights into repeat instability: Role of RNA•DNA hybrids. RNA Biol. 2010, 7 (5): 551–8. PMC 3073251 . PMID 20729633. doi:10.4161/rna.7.5.12745.

[pmid25608779-5] 4.0 ^4.1 ^4.2 Usdin K, House NC, Freudenreich CH. Repeat instability during DNA repair: Insights from model systems. Crit. Rev. Biochem. Mol. Biol. 2015, 50 (2): 142–67. PMC 4454471 . PMID 25608779. doi:10.3109/10409238.2014.999192.

[6] News Release, Weizmann Institute of Science, "Scientists at the Weizmann Institute, using computer simulations, have provided an explanation as to why certain genetic diseases caused by repeats in the code are 「genetic time-bombs」 whose onset and progression can be accurately predicted," November 21, 2007, at http://80.70.129.162/site/en/weizman.asp?pi=371&doc_id=5042 （頁面存檔備份，存於網際網路檔案館）. Retrieved on 2007-12-30.

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