Abstract
Alkylated DNA lesions, induced by both exogenous chemical agents and endogenous metabolites, represent a major form of DNA damage in cells. The repair of alkylation damage is critical in all cells because such damage is cytotoxic and potentially mutagenic. Alkylation chemotherapy is a major therapeutic modality for many tumors, underscoring the importance of the repair pathways in cancer cells. Several different pathways exist for alkylation repair, including base excision and nucleotide excision repair, direct reversal by methyl-guanine methyltransferase (MGMT), and dealkylation by the AlkB homolog (ALKBH) protein family. However, maintaining a proper balance between these pathways is crucial for the favorable response of an organism to alkylating agents. Here, we summarize the progress in the field of DNA alkylation lesion repair and describe the implications for cancer chemotherapy.
概要
DNA烷基化损伤作为细胞内一种主要的DNA损伤形式,可由外源性化学试剂和内源性代谢物诱导发生。DNA烷基化损伤具有细胞毒性并可能诱导突变,因此烷基化损伤修复在所有细胞内都至关重要。同时,烷基化肿瘤化学疗法是许多肿瘤的主要治疗方案,这也强调了癌细胞内烷基化修复途径的重要性。烷基化修复的途径包括碱基切除和核苷酸切除修复、甲基鸟嘌呤甲基转移酶(MGMT)的直接逆转以及ALKBH蛋白家族的脱烷基化作用。然而,这些修复途径之间的内部平衡才是机体有效应答DNA烷基化试剂的关键所在。在这里,我们总结了DNA烷基化损伤修复领域的进展,并进一步描述该领域的研究对肿瘤化疗的深刻意义。
Similar content being viewed by others
Change history
08 April 2021
The typesetting format of the online version of the first issue (2021 22(01)) of Journal of Zhejiang University-SCIENCE B is different from that of the printed version (but all the text, figure and table contents in the article are correct). This is due to the new typesetting company adopted this year.
References
Aas PA, Otterlei M, Falnes PØ, et al., 2003. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature, 421(6925):859–863. https://doi.org/10.1038/nature01363
Asagoshi K, Liu Y, Masaoka A, et al., 2010. DNA polymerase β-dependent long patch base excision repair in living cells. DNA Repair (Amst), 9(2):109–119. https://doi.org/10.1016/j.dnarep.2009.11.002
Bapat A, Fishel ML, Kelley MR, 2009. Going Ape as an approach to cancer therapeutics. Antioxid Redox Signal, 11(3): 651–667. https://doi.org/10.1089/ARS.2008.2218
Bapat A, Glass LS, Luo MH, et al., 2010. Novel small-molecule inhibitor of apurinic/apyrimidinic endonuclease 1 blocks proliferation and reduces viability of glioblastoma cells. J Pharmacol Exp Ther, 334(3):988–998. https://doi.org/10.1124/jpet.110.169128
Barrows LR, Magee PN, 1982. Nonenzymatic methylation of DNA by S-adenosylmethionine in vitro. Carcinogenesis, 3(3):349–351. https://doi.org/10.1093/carcin/3.3.349
Beranek DT, 1990. Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. Mutat Res, 231(1): 11–30. https://doi.org/10.1016/0027-5107(90)90173-2
Bjørås KØ, Sousa MML, Sharma A, et al., 2017. Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication. Nucleic Acids Res, 45(14):8291–8301. https://doi.org/10.1093/nar/gkx476
Bobola MS, Finn LS, Ellenbogen RG, et al., 2005. Apurinic/apyrimidinic endonuclease activity is associated with response to radiation and chemotherapy in medulloblastoma and primitive neuroectodermal tumors. Clin Cancer Res, 11(20):7405–7414. https://doi.org/10.1158/1078-0432.CCR-05-1068
Brickner JR, Soll JM, Lombardi PM, et al., 2017. A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair. Nature, 551(7680):389–393. https://doi.org/10.1038/nature24484
Brickner JR, Townley BA, Mosammaparast N, 2019. Intersections between transcription-coupled repair and alkylation damage reversal. DNA Repair (Amst), 81:102663. https://doi.org/10.1016/j.dnarep.2019.102663
Butler M, Pongor L, Su YT, et al., 2020. MGMT status as a clinical biomarker in glioblastoma. Trends Cancer, 6(5): 380–391. https://doi.org/10.1016/j.trecan.2020.02.010
Calvo JA, Meira LB, Lee CYI, et al., 2012. DNA repair is indispensable for survival after acute inflammation. J Clin Invest, 122(7):2680–2689. https://doi.org/10.1172/JCI63338
Chen FY, Bian K, Tang Q, et al., 2017. Oncometabolites d-and l-2-hydroxyglutarate inhibit the AlkB family DNA repair enzymes under physiological conditions. Chem Res Toxicol, 30(4): 1102–1110. https://doi.org/10.1021/acs.chemrestox.7b00009
Chen ZJ, Qi MJ, Shen B, et al., 2019. Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs. Nucleic Acids Res, 47(5): 2533–2545. https://doi.org/10.1093/nar/gky1250
Christmann M, Verbeek B, Roos WP, et al., 2011. O6-methylguanine-DNA methyltransferase (MGMT) in normal tissues and tumors: enzyme activity, promoter methylation and immunohistochemistry. Biochim Biophys Acta, 1816(2): 179–190. https://doi.org/10.1016/j.bbcan.2011.06.002
Coquerelle T, Dosch J, Kaina B, 1995. Overexpression of N-methylpurine-DNA glycosylase in Chinese hamster ovary cells renders them more sensitive to the production of chromosomal aberrations by methylating agents—a case of imbalanced DNA repair. Mutat Res, 336(1):9–17. https://doi.org/10.1016/0921-8777(94)00035-5
Corbett MA, Dudding-Byth T, Crock PA, et al., 2015. A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A. J Med Genet, 52(4):269–274. https://doi.org/10.1136/jmedgenet-2014-102418
Dai XX, Wang TL, Gonzalez G, et al., 2018. Identification of YTH domain-containing proteins as the readers for N1-methyladenosine in RNA. Anal Chem, 90(11):6380–6384. https://doi.org/10.1021/acs.analchem.8b01703
Dango S, Mosammaparast N, Sowa ME, et al., 2011. DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. Mol Cell, 44(3):373–384. https://doi.org/10.1016/j.molcel.2011.08.039
Deans AJ, West SC, 2011. DNA interstrand crosslink repair and cancer. Nat Rev Cancer, 11(7):467–480. https://doi.org/10.1038/nrc3088
de Murcia JM, Niedergang C, Trucco C, et al., 1997. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci USA, 94(14):7303–7307. https://doi.org/10.1073/pnas.94.14.7303
Dominissini D, Nachtergaele S, Moshitch-Moshkovitz S, et al., 2016. The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA. Nature, 530(7591):441–446. https://doi.org/10.1038/nature16998
Drabløs F, Feyzi E, Aas PA, et al., 2004. Alkylation damage in DNA and RNA—repair mechanisms and medical significance. DNA Repair (Amst), 3(11):1389–1407. https://doi.org/10.1016/j.dnarep.2004.05.004
Dumenco LL, Allay E, Norton K, et al., 1993. The prevention of thymic lymphomas in transgenic mice by human O6-alkylguanine-DNA alkyltransferase. Science, 259(5092): 219–222. https://doi.org/10.1126/science.8421782
Dumitrache LC, Shimada M, Downing SM, et al., 2018. Apurinic endonuclease-1 preserves neural genome integrity to maintain homeostasis and thermoregulation and prevent brain tumors. Proc Natl Acad Sci USA, 115(52): E12285–E12294. https://doi.org/10.1073/pnas.1809682115
Duncan T, Trewick SC, Koivisto P, et al., 2002. Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci USA, 99(26):16660–16665. https://doi.org/10.1073/pnas.262589799
Engelward BP, Weeda G, Wyatt MD, et al., 1997. Base excision repair deficient mice lacking the aag alkyladenine DNA glycosylase. Proc Natl Acad Sci USA, 94(24): 13087–13092. https://doi.org/10.1073/pnas.94.24.13087
Esteller M, Garcia-Foncillas J, Andion E, et al., 2000. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med, 343(19):1350–1354. https://doi.org/10.1056/NEJM200011093431901
Fan JS, Wilson PF, Wong HK, et al., 2007. XRCC1 down-regulation in human cells leads to DNA-damaging agent hypersensitivity, elevated sister chromatid exchange, and reduced survival of BRCA2 mutant cells. Environ Mol Mutagen, 48(6):491–500. https://doi.org/10.1002/em.20312
Feng JA, Crasto CJ, Matsumoto Y, 1998. Deoxyribose phosphate excision by the N-terminal domain of the polymerase β: the mechanism revisited. Biochemistry, 37(27):9605–9611. https://doi.org/10.1021/bi9808619
Fu D, Calvo JA, Samson LD, 2012. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat Rev Cancer, 12(2):104–120. https://doi.org/10.1038/nrc3185
Fu D, Samson LD, Hübscher U, et al., 2015. The interaction between ALKBH2 DNA repair enzyme and PCNA is direct, mediated by the hydrophobic pocket of PCNA and perturbed in naturally-occurring ALKBH2 variants. DNA Repair (Amst), 35:13–18. https://doi.org/10.1016/j.dnarep.2015.09.008
Fu SJ, Li Z, Xiao LB, et al., 2019. Glutamine synthetase promotes radiation resistance via facilitating nucleotide metabolism and subsequent DNA damage repair. Cell Rep, 28(5):1136–1143.e4. https://doi.org/10.1016/j.celrep.2019.07.002
Fukushima T, Katayama Y, Watanabe T, et al., 2005. Promoter hypermethylation of mismatch repair gene HMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea. Clin Cancer Res, 11(4): 1539–1544. https://doi.org/10.1158/1078-0432.CCR-04-1625
Gentil A, Cabral-Neto JB, Mariage-Samson R, et al., 1992. Mutagenicity of a unique apurinic/apyrimidinic site in mammalian cells. J Mol Biol, 227(4):981–984. https://doi.org/10.1016/0022-2836(92)90513-j
Germano G, Lamba S, Rospo G, et al., 2017. Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth. Nature, 552(7683):116–120. https://doi.org/10.1038/nature24673
Gilljam KM, Feyzi E, Aas PA, et al., 2009. Identification of a novel, widespread, and functionally important PCNA-binding motif. J Cell Biol, 186(5):645–654. https://doi.org/10.1083/jcb.200903138
Glassner BJ, Weeda G, Allan JM, et al., 1999. DNA repair methyltransferase (MGMT) knockout mice are sensitive to the lethal effects of chemotherapeutic alkylating agents. Mutagenesis, 14(3):339–347. https://doi.org/10.1093/mutage/14.3.339
Hegi ME, Diserens AC, Gorlia T, et al., 2005. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med, 352(10):997–1003. https://doi.org/10.1056/NEJMoa043331
Hoch NC, Hanzlikova H, Rulten SL, et al., 2017. XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia. Nature, 541(7635):87–91. https://doi.org/10.1038/nature20790
Hofseth LJ, Khan MA, Ambrose M, et al., 2003. The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation. J Clin Invest, 112(12):1887–1894. https://doi.org/10.1172/JCI19757
Hong HZ, Cao HC, Wang YS, 2007. Formation and genotoxicity of a guanine-cytosine intrastrand cross-link lesion in vivo. Nucleic Acids Res, 35(21):7118–7127. https://doi.org/10.1093/nar/gkm851
Hori H, 2014. Methylated nucleosides in tRNA and tRNA methyltransferases. Front Genet, 5:144. https://doi.org/10.3389/fgene.2014.00144
Horton JK, Joyce-Gray DF, Pachkowski BF, et al., 2003. Hypersensitivity of DNA polymerase β null mouse fibroblasts reflects accumulation of cytotoxic repair intermediates from site-specific alkyl DNA lesions. DNA Repair (Amst), 2(1):27–48. https://doi.org/10.1016/s1568-7864(02)00184-2
Hunter C, Smith R, Cahill DP, et al., 2006. A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res, 66(8):3987–3991. https://doi.org/10.1158/0008-5472.CAN-06-0127
Huttlin EL, Bruckner RJ, Paulo JA, et al., 2017. Architecture of the human interactome defines protein communities and disease networks. Nature, 545(7655):505–509. https://doi.org/10.1038/nature22366
Jacobs AL, Schär P, 2012. DNA glycosylases: in DNA repair and beyond. Chromosoma, 121(1):1–20. https://doi.org/10.1007/s00412-011-0347-4
Jaiswal AS, Banerjee S, Panda H, et al., 2009. A novel inhibitor of DNA polymerase β enhances the ability of temozolomide to impair the growth of colon cancer cells. Mol Cancer Res, 7(12):1973–1983. https://doi.org/10.1158/1541-7786.MCR-09-0309
Jaiswal AS, Banerjee S, Aneja R, et al., 2011. DNA polymerase β as a novel target for chemotherapeutic intervention of colorectal cancer. PLoS ONE, 6(2):e16691. https://doi.org/10.1371/journal.pone.0016691
Jelezcova E, Trivedi RN, Wang XH, et al., 2010. Parp1 activation in mouse embryonic fibroblasts promotes Pol β-dependent cellular hypersensitivity to alkylation damage. Mutat Res, 686(1–2):57–67. https://doi.org/10.1016/j.mrfmmm.2010.01.016
Jiang J, Zhang XQ, Yang HM, et al., 2009. Polymorphisms of DNA repair genes: ADPRT, XRCC1, and XPD and cancer risk in genetic epidemiology. In: Verma M (Ed.), Cancer Epidemiology. Humana Press, New York, p.305–333. https://doi.org/10.1007/978-1-59745-416-2_16
Johnson RE, Yu SL, Prakash S, et al., 2007. A role for yeast and human translesion synthesis DNA polymerases in promoting replication through 3-methyl adenine. Mol Cell Biol, 27(20):7198–7205. https://doi.org/10.1128/MCB.01079-07
Kaina B, Christmann M, Naumann S, et al., 2007. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst), 6(8):1079–1099. https://doi.org/10.1016/j.dnarep.2007.03.008
Kawate H, Itoh R, Sakumi K, et al., 2000. A defect in a single allele of the Mlh1 gene causes dissociation of the killing and tumorigenic actions of an alkylating carcinogen in methyltransferase-deficient mice. Carcinogenesis, 21(2): 301–305. https://doi.org/10.1093/carcin/21.2.301
Kietrys AM, Velema WA, Kool ET, 2017. Fingerprints of modified RNA bases from deep sequencing profiles. J Am Chem Soc, 139(47):17074–17081. https://doi.org/10.1021/jacs.7b07914
Klapacz J, Meira LB, Luchetti DG, et al., 2009. O6-methylguanine-induced cell death involves exonuclease 1 as well as DNA mismatch recognition in vivo. Proc Natl Acad Sci USA, 106(2):576–581. https://doi.org/10.1073/pnas.0811991106
Klapacz J, Lingaraju GM, Guo HH, et al., 2010. Frameshift mutagenesis and microsatellite instability induced by human alkyladenine DNA glycosylase. Mol Cell, 37(6): 843–853. https://doi.org/10.1016/j.molcel.2010.01.038
Konishi N, Nakamura M, Ishida E, et al., 2005. High expression of a new marker PCA-1 in human prostate carcinoma. Clin Cancer Res, 11(14):5090–5097. https://doi.org/10.1158/1078-0432.CCR-05-0195
Larson K, Sahm J, Shenkar R, et al., 1985. Methylationinduced blocks to in vitro DNA replication. Mutat Res, 150(1–2):77–84. https://doi.org/10.1016/0027-5107(85)90103-4
Li XY, Xiong XS, Wang K, et al., 2016. Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome. Nat Chem Biol, 12(5):311–316. https://doi.org/10.1038/nchembio.2040
Lin DP, Wang YX, Scherer SJ, et al., 2004. An Msh2 point mutation uncouples DNA mismatch repair and apoptosis. Cancer Res, 64(2):517–522. https://doi.org/10.1158/0008-5472.can-03-2957
Lindahl T, 1993. Instability and decay of the primary structure of DNA. Nature, 362(6422):709–715. https://doi.org/10.1038/362709a0
Liu L, Allay E, Dumenco LL, et al., 1994. Rapid repair of O6-methylguanine-DNA adducts protects transgenic mice from N-methylnitrosourea-induced thymic lymphomas. Cancer Res, 54(17):4648–4652.
Liu LL, Gerson SL, 2004. Therapeutic impact of methoxyamine: blocking repair of abasic sites in the base excision repair pathway. Curr Opin Investig Drugs, 5(6):623–627.
Liu Y, Prasad R, Wilson SH, 2010. HMGB1: roles in base excision repair and related function. Biochim Biophys Acta, 1799(1–2):119–130. https://doi.org/10.1016/j.bbagrm.2009.11.008
Luo CY, Hajkova P, Ecker JR, 2018. Dynamic DNA methylation: in the right place at the right time. Science, 361(6409):1336–1340. https://doi.org/10.1126/science.aat6806
McFaline-Figueroa JL, Braun CJ, Stanciu M, et al., 2015. Minor changes in expression of the mismatch repair protein MSH2 exert a major impact on glioblastoma response to temozolomide. Cancer Res, 75(15):3127–3138. https://doi.org/10.1158/0008-5472.CAN-14-3616
Mehta KPM, Lovejoy CA, Zhao RX, et al., 2020. HMCES maintains replication fork progression and prevents doublestrand breaks in response to APOBEC deamination and abasic site formation. Cell Rep, 31(9):107705. https://doi.org/10.1016/j.celrep.2020.107705
Meira LB, Bugni JM, Green SL, et al., 2008. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J Clin Invest, 118(7):2516–2525. https://doi.org/10.1172/JCI35073
Mohan M, Akula D, Dhillon A, et al., 2019. Human RAD51 paralogue RAD51C fosters repair of alkylated DNA by interacting with the ALKBH3 demethylase. Nucleic Acids Res, 47(22):11729–11745. https://doi.org/10.1093/nar/gkz938
Mohni KN, Wessel SR, Zhao RX, et al., 2019. HMCES maintains genome integrity by shielding abasic sites in singlestrand DNA. Cell, 176(1–2):144–153.e13. https://doi.org/10.1016/j.cell.2018.10.055
Mojas N, Lopes M, Jiricny J, 2007. Mismatch repair-dependent processing of methylation damage gives rise to persistent single-stranded gaps in newly replicated DNA. Genes Dev, 21(24):3342–3355. https://doi.org/10.1101/gad.455407
Montaldo NP, Bordin DL, Brambilla A, et al., 2019. Alkyladenine DNA glycosylase associates with transcription elongation to coordinate DNA repair with gene expression. Nat Commun, 10:5460. https://doi.org/10.1038/s41467-019-13394-w
Morales JC, Kool ET, 1999. Minor groove interactions between polymerase and DNA: more essential to replication than Watson-Crick hydrogen bonds? J Am Chem Soc, 121(10):2323–2324. https://doi.org/10.1021/ja983502+
Naryshkin N, Revyakin A, Kim Y, et al., 2000. Structural organization of the RNA polymerase-promoter open complex. Cell, 101(6):601–611. https://doi.org/10.1016/s0092-8674(00)80872-7
Odell ID, Barbour JE, Murphy DL, et al., 2011. Nucleosome disruption by DNA ligase III-XRCC1 promotes efficient base excision repair. Mol Cell Biol, 31(22):4623–4632. https://doi.org/10.1128/MCB.05715-11
Odell ID, Wallace SS, Pederson DS, 2013. Rules of engagement for base excision repair in chromatin. J Cell Physiol, 228(2):258–266. https://doi.org/10.1002/jcp.24134
Olmon ED, Delaney S, 2017. Differential ability of five DNA glycosylases to recognize and repair damage on nucleosomal DNA. ACS Chem Biol, 12(3):692–701. https://doi.org/10.1021/acschembio.6b00921
Pilžys T, Marcinkowski M, Kukwa W, et al., 2019. ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy. Sci Rep, 9:13249. https://doi.org/10.1038/s41598-019-49550-x
Poltoratsky V, Horton JK, Prasad R, et al., 2005. REV1 mediated mutagenesis in base excision repair deficient mouse fibroblast. DNA Repair (Amst), 4(10):1182–1188. https://doi.org/10.1016/j.dnarep.2005.05.002
Prasad R, Liu Y, Deterding LJ, et al., 2007. HMGB1 is a cofactor in mammalian base excision repair. Mol Cell, 27(5): 829–841. https://doi.org/10.1016/j.molcel.2007.06.029
Quiros S, Roos WP, Kaina B, 2010. Processing of O6-methylguanine into DNA double-strand breaks requires two rounds of replication whereas apoptosis is also induced in subsequent cell cycles. Cell Cycle, 9(1):168–178. https://doi.org/10.4161/cc.9.1.10363
Ringvoll J, Nordstrand LM, Vågbø CB, et al., 2006. Repair deficient mice reveal mABH2 as the primary oxidative demethylase for repairing 1meA and 3meC lesions in DNA. EMBO J, 25(10):2189–2198. https://doi.org/10.1038/sj.emboj.7601109
Rodriguez Y, Smerdon MJ, 2013. The structural location of DNA lesions in nucleosome core particles determines accessibility by base excision repair enzymes. J Biol Chem, 288(19):13863–13875. https://doi.org/10.1074/jbc.M112.441444
Rodriguez Y, Howard MJ, Cuneo MJ, et al., 2017. Unencumbered Pol β lyase activity in nucleosome core particles. Nucleic Acids Res, 45(15):8901–8915. https://doi.org/10.1093/nar/gkx593
Roos W, Baumgartner M, Kaina B, 2004. Apoptosis triggered by DNA damage O6-methylguanine in human lymphocytes requires DNA replication and is mediated by p53 and Fas/CD95/Apo-1. Oncogene, 23(2):359–367. https://doi.org/10.1038/sj.onc.1207080
Rouleau M, Patel A, Hendzel MJ, et al., 2010. PARP inhibition: PARP1 and beyond. Nat Rev Cancer, 10(4):293–301. https://doi.org/10.1038/nrc2812
Rydberg B, Lindahl T, 1982. Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-L-methionine is a potentially mutagenic reaction. EMBO J, 1(2):211–216. https://doi.org/10.1002/j.1460-2075.1982.tb01149.x
Safra M, Sas-Chen A, Nir R, et al., 2017. The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution. Nature, 551(7679):251–255. https://doi.org/10.1038/nature24456
Saha D, Rabkin SD, Martuza RL, 2020. Temozolomide antagonizes oncolytic immunovirotherapy in glioblastoma. J Immunother Cancer, 8(1):e000345. https://doi.org/10.1136/jitc-2019-000345
Seo KW, Kleiner RE, 2020. YTHDF2 recognition of N1-methyladenosine (m1A)-modified RNA is associated with transcript destabilization. ACS Chem Biol, 15(1): 132–139. https://doi.org/10.1021/acschembio.9b00655
Shibata A, Kamada N, Masumura KI, et al., 2005. Parp-1 deficiency causes an increase of deletion mutations and insertions/rearrangements in vivo after treatment with an alkylating agent. Oncogene, 24(8):1328–1337. https://doi.org/10.1038/sj.onc.1208289
Shrivastav N, Li D, Essigmann JM, 2010. Chemical biology of mutagenesis and DNA repair: cellular responses to DNA alkylation. Carcinogenesis, 31(1):59–70. https://doi.org/10.1093/carcin/bgp262
Sobol RW, Horton JK, Kühn R, et al., 1996. Requirement of mammalian DNA polymerase- β in base-excision repair. Nature, 379(6561):183–186. https://doi.org/10.1038/379183a0
Sobol RW, Prasad R, Evenski A, et al., 2000. The lyase activity of the DNA repair protein β-polymerase protects from DNA-damage-induced cytotoxicity. Nature, 405(6788): 807–810. https://doi.org/10.1038/35015598
Soll JM, Sobol RW, Mosammaparast N, 2017. Regulation of DNA alkylation damage repair: lessons and therapeutic opportunities. Trends Biochem Sci, 42(3):206–218. https://doi.org/10.1016/j.tibs.2016.10.001
Soll JM, Brickner JR, Mudge MC, et al., 2018. RNA ligase-like domain in activating signal cointegrator 1 complex subunit 1 (ASCC1) regulates ASCC complex function during alkylation damage. J Biol Chem, 293(35):13524–13533. https://doi.org/10.1074/jbc.RA117.000114
Sossou M, Flohr-Beckhaus C, Schulz I, et al., 2005. APE1 overexpression in XRCC1-deficient cells complements the defective repair of oxidative single strand breaks but increases genomic instability. Nucleic Acids Res, 33(1): 298–306. https://doi.org/10.1093/nar/gki173
Starcevic D, Dalal S, Sweasy JB, 2004. Is there a link between DNA polymerase β and cancer? Cell Cycle, 3(8):996–999. https://doi.org/10.4161/cc.3.8.1062
Stefansson OA, Hermanowicz S, van der Horst J, et al., 2017. CpG promoter methylation of the ALKBH3 alkylation repair gene in breast cancer. BMC Cancer, 17:469. https://doi.org/10.1186/s12885-017-3453-8
Ströbel T, Madlener S, Tuna S, et al., 2017. Ape1 guides DNA repair pathway choice that is associated with drug tolerance in glioblastoma. Sci Rep, 7:9674. https://doi.org/10.1038/s41598-017-10013-w
Sun GH, Zhao LJ, Zhong RG, et al., 2018. The specific role of O6-methylguanine-DNA methyltransferase inhibitors in cancer chemotherapy. Future Med Chem, 10(16): 1971–1996. https://doi.org/10.4155/fmc-2018-0069
Svilar D, Goellner EM, Almeida KH, et al., 2011. Base excision repair and lesion-dependent subpathways for repair of oxidative DNA damage. Antioxid Redox Signal, 14(12): 2491–2507. https://doi.org/10.1089/ars.2010.3466
Tasaki M, Shimada K, Kimura H, et al., 2011. ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer. Br J Cancer, 104(4):700–706. https://doi.org/10.1038/sj.bjc.6606012
Taverna P, Liu LL, Hwang HS, et al., 2001. Methoxyamine potentiates DNA single strand breaks and double strand breaks induced by temozolomide in colon cancer cells. Mutat Res, 485(4):269–281. https://doi.org/10.1016/s0921-8777(01)00076-3
Tran TQ, Ishak Gabra MB, Lowman XH, et al., 2017. Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes. PLoS Biol, 15(11):e2002810. https://doi.org/10.1371/journal.pbio.2002810
Tsuzuki T, Kawate H, Iwakuma T, 1998. Study on carcinogenesis and mutation suppression: repair of alkylation DNA damage and suppression of tumors. Fukuoka Igaku Zasshi, 89(1):1–10.
Ueda Y, Ooshio I, Fusamae Y, et al., 2017. AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells. Sci Rep, 7:42271. https://doi.org/10.1038/srep42271
Wang P, Wu J, Ma SH, et al., 2015. Oncometabolite d-2-hydroxyglutarate inhibits ALKBH DNA repair enzymes and sensitizes IDH mutant cells to alkylating agents. Cell Rep, 13(11):2353–2361. https://doi.org/10.1016/j.celrep.2015.11.029
Wang X, Lu ZK, Gomez A, et al., 2014. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature, 505(7481):117–120. https://doi.org/10.1038/nature12730
Warren JJ, Forsberg LJ, Beese LS, 2006. The structural basis for the mutagenicity of O6-methylguanine lesions. Proc Natl Acad Sci USA, 103(52):19701–19706. https://doi.org/10.1073/pnas.0609580103
Watanabe S, Ichimura T, Fujita N, et al., 2003. Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin. Proc Natl Acad Sci USA, 100(22):12859–12864. https://doi.org/10.1073/pnas.2131819100
Westdorp H, Fennemann FL, Weren RDA, et al., 2016. Opportunities for immunotherapy in microsatellite instable colorectal cancer. Cancer Immunol Immunother, 65(10):1249–1259. https://doi.org/10.1007/s00262-016-1832-7
Xie CR, Sheng HS, Zhang N, et al., 2016. Association of MSH6 mutation with glioma susceptibility, drug resistance and progression. Mol Clin Oncol, 5(2):236–240. https://doi.org/10.3892/mco.2016.907
Yang GZ, Scherer SJ, Shell SS, et al., 2004. Dominant effects of an Msh6 missense mutation on DNA repair and cancer susceptibility. Cancer Cell, 6(2):139–150. https://doi.org/10.1016/j.ccr.2004.06.024
York SJ, Modrich P, 2006. Mismatch repair-dependent iterative excision at irreparable O6-methylguanine lesions in human nuclear extracts. J Biol Chem, 281(32):22674–22683. https://doi.org/10.1074/jbc.M603667200
Yoshioka KI, Yoshioka Y, Hsieh P, 2006. ATR kinase activation mediated by MutSα and MutLα in response to cytotoxic O6-methylguanine adducts. Mol Cell, 22(4):501–510. https://doi.org/10.1016/j.molcel.2006.04.023
Yuan CL, He F, Ye JZ, et al., 2017. APE1 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis. Oncotarget, 8(35):59720–59728. https://doi.org/10.18632/oncotarget.19814
Zhang C, Jia GF, 2018. Reversible RNA modification N1-methyladenosine (m1A) in mRNA and tRNA. Genomics Proteomics Bioinformatics, 16(3): 155–161. https://doi.org/10.1016/j.gpb.2018.03.003
Zhao BS, Roundtree IA, He C, 2017. Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol, 18(1):31–42. https://doi.org/10.1038/nrm.2016.132
Author information
Authors and Affiliations
Contributions
Yihan PENG wrote and edited the manuscript; Huadong PEI designed the study and revised the manuscript. Both authors have read and approved the final manuscript. Therefore, both authors have full access to the data in the study and take responsibility for the integrity and security of the data.
Corresponding author
Additional information
Compliance with ethics guidelines
Yihan PENG and Huadong PEI declare they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by either of the authors.
Rights and permissions
About this article
Cite this article
Peng, Y., Pei, H. DNA alkylation lesion repair: outcomes and implications in cancer chemotherapy. J. Zhejiang Univ. Sci. B 22, 47–62 (2021). https://doi.org/10.1631/jzus.B2000344
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B2000344