鹼基切除修復

鹼基切除修復（Base excision repair，BER）是細胞修復受損DNA的一種機制，主要用來修補大小較小、對DNA雙股螺旋結構影響較小的損傷，包括去胺、被烷基化或氧化的鹼基，如8-羥基鳥嘌呤（英語：8-Oxoguanine）（8-oxoG）、7-甲基鳥苷、黃嘌呤與尿嘧啶等^[1][2]。大小較大、影響DNA結構較大的損傷（如紫外線造成的胸腺嘧啶二聚體）則是由核苷酸切除修復（NER）途徑修補^[3]。細菌^[4]、古菌^[5]與真核生物皆有鹼基切除修復的機制。

鹼基切除修復（BER）示意圖

BER的過程首先由DNA糖基酶（英語：DNA glycosylase）移除損傷的鹼基，形成AP位點，隨後AP核酸內切酶（英語：AP endonuclease）將此位點的磷酸二酯鍵切除，造成DNA單股斷裂，接著再由DNA聚合酶合成缺失的鹼基（與一般DNA複製的過程一樣有DNA夾參與），可能僅合成單一缺失的鹼基後由DNA連接酶完成修補（短補丁修復；short-patch BER），也可能合成2-10個核苷酸以取代下游的若干的核苷酸，由Flap核酸內切酶（英語：Flap endonuclease）將舊有的核苷酸切除後，再由DNA連接酶完成修補（長補丁修復；long-patch BER）^[6]，兩途徑的選擇由DNA損傷種類、細胞週期、細胞分化狀態與物種種類等因素決定^[7]。

DNA糖基酶的活性可能隨老化而下降，使BER途徑的效率降低^[8]。另外BER途徑的缺失與數種癌症有關^[9][10]。

參考文獻

• 分子與細胞生物學主題

1. Dasari, A.; Choi, J.-S.; Berdis, A.J. Chemotherapeutic intervention by inhibiting DNA polymerases. DNA Repair in Cancer Therapy (Second Edition). 2016: 179–224. doi:10.1016/B978-0-12-803582-5.00007-3.
2. Jayanta Chaudhuri; Frederick W. Alt. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nature Reviews Immunology. 2004, 4 (7): 541–552. PMID 15229473. doi:10.1038/nri1395.
3. Reardon JT, Sancar A. Purification and characterization of Escherichia coli and human nucleotide excision repair enzyme systems. Methods in Enzymology. 2006, 408: 189–213. ISBN 9780121828134. PMID 16793370. doi:10.1016/S0076-6879(06)08012-8.
4. Wallace SS. Base excision repair: a critical player in many games.. DNA Repair (Amst). 2014, 19: 14–26. PMC 4100245 . PMID 24780558. doi:10.1016/j.dnarep.2014.03.030.
5. Grasso S, Tell G. Base excision repair in Archaea: back to the future in DNA repair.. DNA Repair (Amst). 2014, 21: 148–57. PMID 25012975. doi:10.1016/j.dnarep.2014.05.006.
6. Liu Y, Prasad R, Beard WA, Kedar PS, Hou EW, Shock DD, Wilson SH. Coordination of Steps in Single-nucleotide Base Excision Repair Mediated by Apurinic/Apyrimidinic Endonuclease 1 and DNA Polymerase β. Journal of Biological Chemistry. 2007, 282 (18): 13532–13541. PMC 2366199 . PMID 17355977. doi:10.1074/jbc.M611295200.
7. Fortini P, Dogliotti E. Base damage and single-strand break repair: mechanisms and functional significance of short- and long-patch repair subpathways. DNA Repair. April 2007, 6 (4): 398–409. PMID 17129767. doi:10.1016/j.dnarep.2006.10.008.
8. Atamna H, Cheung I, Ames BN. A method for detecting abasic sites in living cells: age-dependent changes in base excision repair. Proc. Natl. Acad. Sci. U.S.A. 2000, 97 (2): 686–91. PMC 15391 . PMID 10639140. doi:10.1073/pnas.97.2.686.
9. Chaisaingmongkol J, Popanda O, Warta R, Dyckhoff G, Herpel E, Geiselhart L, Claus R, Lasitschka F, Campos B, Oakes CC, Bermejo JL, Herold-Mende C, Plass C, Schmezer P. Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma. Oncogene. 2012, 31 (49): 5108–16. PMID 22286769. doi:10.1038/onc.2011.660.
10. Farrington, S. M.; Tenesa, A; Barnetson, R; Wiltshire, A; Prendergast, J; Porteous, M; Campbell, H; Dunlop, M. G. Germline susceptibility to colorectal cancer due to base-excision repair gene defects. The American Journal of Human Genetics. 2005, 77 (1): 112–9. PMC 1226182 . PMID 15931596. doi:10.1086/431213.