Non-homologous functions of the AlkB homologs

Journal of Molecular Cell Biology

Volumn 7, Issue 6, 2015, Pages 494-504

  Ougland, Rune ^a   Rognes, Torbjørn ^a,b   Klungland, Arne ^a,c   Larsen, Elisabeth ^a  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

^c UNIVERSITY OF OSLO   (Norway)

Author keywords

AlkB homologs; ALKBH; DNA repair; Epigenetics; Histone demethylation; RNA repair; TRNA modification

Indexed keywords

ALKB; DNA LIGASE; UNCLASSIFIED DRUG; 2 OXOGLUTARIC ACID; ALKB PROTEIN, E COLI; ALPHA-KETOGLUTARIC ACID; DIOXYGENASE; ESCHERICHIA COLI PROTEIN; MIXED FUNCTION OXIDASE; TRANSFER RNA;

ALKBH1 GENE; ALKBH2 GENE; ALKBH3 GENE; ALKBH4 GENE; ALKBH5 GENE; ALKBH8 GENE; ALKBH9 GENE; BACTERIAL GENE; DEMETHYLATION; DNA METHYLATION; DNA REPAIR; ENZYME ANALYSIS; EPIGENETICS; GENE FUNCTION; HUMAN; MORBIDITY; MORTALITY; NONHUMAN; PHENOTYPE; PHYLOGENETIC TREE; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN METHYLATION; REVIEW; RNA METHYLATION; ANIMAL; BIOLOGY; CHEMISTRY; CLASSIFICATION; ENZYME SPECIFICITY; METABOLISM; MOUSE; PHYLOGENY; PHYSIOLOGY; PROTEIN PROCESSING; RNA PROCESSING; SEQUENCE HOMOLOGY;

ANIMALS; COMPUTATIONAL BIOLOGY; DIOXYGENASES; DNA METHYLATION; DNA REPAIR; ESCHERICHIA COLI PROTEINS; HUMANS; KETOGLUTARIC ACIDS; MICE; MIXED FUNCTION OXYGENASES; PHYLOGENY; PROTEIN PROCESSING, POST-TRANSLATIONAL; RNA PROCESSING, POST-TRANSCRIPTIONAL; RNA, TRANSFER; SEQUENCE HOMOLOGY, AMINO ACID; SUBSTRATE SPECIFICITY;

EID: 84975691137     PISSN: 16742788     EISSN: 17594685     Source Type: Journal    
DOI: 10.1093/jmcb/mjv029     Document Type: Review

References (124)

1. Aas, P.A., Otterlei, M., Falnes, P.O., et al. (2003). Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 421, 859-863.
2. Adamo, A., Barrero, M.J., and Izpisua Belmonte, J.C. (2011a). LSD1 and pluripotency: a new player in the network. Cell Cycle 10, 3215-3216.
3. Adamo, A., Sese, B., Boue, S., et al. (2011b). LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells. Nat. Cell Biol. 13, 652-659.
4. Altschul, S.F., Madden, T.L., Schaffer, A.A., et al. (1997). Gapped BLAST and PSIBLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389-3402.
5. Aravind, L., and Koonin, E.V. (2001). The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate-and iron-dependent dioxygenases. Genome Biol. 2, RESEARCH0007.
6. Batista, P.J., Molinie, B., Wang, J., et al. (2014). m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15, 707-719.
7. Bjornstad, L.G., Zoppellaro, G., Tomter, A.B., et al. (2011). Spectroscopic and magnetic studies of wild-type and mutant forms of the Fe(II)-and 2-oxoglutarate-dependent decarboxylase ALKBH4. Biochem. J. 434, 391-398.
8. Bjornstad, L.G., Meza, T.J., Otterlei, M., et al. (2012). Human ALKBH4 interacts with proteins associated with transcription. PLoS One 7, e49045.
9. Bodi, Z., Button, J.D., Grierson, D., et al. (2010). Yeast targets for mRNA methylation. Nucleic Acids Res. 38, 5327-5335.
10. Boissel, S., Reish, O., Proulx, K., et al. (2009). Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am. J. Hum. Genet. 85, 106-111.
11. Bokar, J.A., Shambaugh, M.E., Polayes, D., et al. (1997). Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA 3, 1233-1247.
12. Boyer, L.A., Lee, T.I., Cole, M.F., et al. (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947-956.
13. Calvo, J.A., Meira, L.B., Lee, C.Y., et al. (2012). DNA repair is indispensable for survival after acute inflammation. J. Clin. Invest. 122, 2680-2689.
14. Cantara, W.A., Crain, P.F., Rozenski, J., et al. (2011). The RNA Modification Database, RNAMDB: 2011 update. Nucleic Acids Res. 39, D195-D201.
15. Carell, T., Brandmayr, C., Hienzsch, A., et al. (2012). Structure and function of noncanonical nucleobases. Angew. Chem. Int. Ed. Engl. 51, 7110-7131.
16. Cetica, V., Genitori, L., Giunti, L., et al. (2009). Pediatric brain tumors: mutations of two dioxygenases (hABH2 and hABH3) that directly repair alkylation damage. J. Neurooncol. 94, 195-201.
17. Chen, B.J., Carroll, P., and Samson, L. (1994). The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity. J. Bacteriol. 176, 6255-6261.
18. Choi, S.Y., Jang, J.H., and Kim, K.R. (2011). Analysis of differentially expressed genes in human rectal carcinoma using suppression subtractive hybridization. Clin. Exp. Med. 11, 219-226.
19. Clancy, M.J., Shambaugh, M.E.,Timpte,C.S., et al. (2002). Inductionof sporulation in Saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene. Nucleic Acids Res. 30, 4509-4518.
20. Dango, S., Mosammaparast, N., Sowa, M.E., et al. (2011). DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. Mol. Cell 44, 373-384.
21. Delaney, J.C., and Essigmann, J.M. (2004). Mutagenesis, genotoxicity, and repair of 1-methyladenine, 3-alkylcytosines, 1-methylguanine, and 3-methylthymine in alkB Escherichia coli. Proc. Natl Acad. Sci. USA 101, 14051-14056.
22. Delaney, J.C., Smeester, L., Wong, C., et al. (2005). AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivo. Nat. Struct. Mol. Biol. 12, 855-860.
23. Dina, C., Meyre, D., Gallina, S., et al. (2007). Variation in FTOcontributes to childhood obesity and severe adult obesity. Nat. Genet. 39, 724-726.
24. Dinglay, S., Trewick, S.C., Lindahl, T., et al. (2000). Defective processing of methylated single-stranded DNA by E. coli AlkB mutants. Genes Dev. 14, 2097-2105.
25. Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., et al. (2012). Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201-206.
26. Drabløs, F., Feyzi, E., Aas, P.A., et al. (2004). Alkylation damage in DNA and RNA - repair mechanisms and medical significance. DNA Repair 3, 1389-1407.
27. Duncan, T., Trewick, S.C., Koivisto, P., et al. (2002). Reversal of DNA alkylation damage by two human dioxygenases. Proc. Natl Acad. Sci. USA 99, 16660-16665.
28. Falnes, P.O. (2004). Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB proteins. Nucleic Acids Res. 32, 6260-6267.
29. Falnes, P.O., Johansen, R.F., and Seeberg, E. (2002). AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature 419, 178-182.
30. Falnes, P.O., Bjoras, M., Aas, P.A., et al. (2004). Substrate specificities of bacterial and human AlkB proteins. Nucleic Acids Res. 32, 3456-3461.
31. Franchini, D.M.,Schmitz,K.M., and Petersen-Mahrt, S.K. (2012).5-Methylcytosine DNA demethylation: more than losing a methyl group. Annu. Rev. Genet. 46, 419-441.
32. Frayling, T.M., Timpson, N.J., Weedon, M.N., et al. (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894.
33. Fu, D., Brophy, J.A., Chan, C.T., et al. (2010a). Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Mol. Cell. Biol. 30, 2449-2459.
34. Fu, Y., Dai, Q., Zhang, W., et al. (2010b). The AlkB domain of mammalian ABH8 catalyzes hydroxylation of 5-methoxycarbonylmethyluridine at the wobble position of tRNA. Angew. Chem. Int. Ed. Engl. 49, 8885-8888.
35. Fu, D., Jordan, J.J., and Samson, L.D. (2013). Human ALKBH7 is required for alkylation and oxidation-induced programmed necrosis. Genes Dev. 27, 1089-1100.
36. Fujii, T., Shimada, K., Anai, S., et al. (2013). ALKBH2, a novel AlkB homologue, contributes to human bladder cancer progression by regulatingMUC1 expression. Cancer Sci. 104, 321-327.
37. Gao,W., Li, L., Xu, P., et al. (2011). Frequent down-regulation of hABH2 in gastric cancer and its involvement in growth of cancer cells. J. Gastroenterol. Hepatol. 26, 577-584.
38. Gerken, T., Girard, C.A., Tung, Y.C., et al. (2007). The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318, 1469-1472.
39. Gilljam, K.M., Feyzi, E., Aas, P.A., et al. (2009). Identification of a novel,widespread, and functionally important PCNA-binding motif. J. Cell Biol. 186, 645-654.
40. Gouy, M., Guindon, S., and Gascuel, O. (2010). SeaView version 4: A multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol. Biol. Evol. 27, 221-224.
41. Harper, J.E., Miceli, S.M., Roberts, R.J., et al. (1990). Sequence specificity of the human mRNA N6-adenosine methylase in vitro. Nucleic Acids Res. 18, 5735-5741.
42. He, C. (2010). Grand challenge commentary: RNA epigenetics? Nat. Chem. Biol. 6, 863-865.
43. Ivanova, N., Dobrin, R., Lu, R., et al. (2006). Dissecting self-renewal in stem cells with RNA interference. Nature 442, 533-538.
44. Iwanami, Y., and Brown, G.M. (1968). Methylated bases of ribosomal ribonucleic acid from HeLa cells. Arch. Biochem. Biophys. 126, 8-15.
45. Jensen, O.N. (2006). Interpreting the protein language using proteomics. Nat. Rev. Mol. Cell Biol. 7, 391-403.
46. Jia, G., Yang, C.G., Yang, S., et al. (2008). Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett. 582, 3313-3319.
47. Jia, G., Fu, Y., Zhao, X., et al. (2011). N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7, 885-887.
48. Johannessen, T.C., Prestegarden, L., Grudic, A., et al. (2013). The DNA repair protein ALKBH2 mediates temozolomide resistance in human glioblastoma cells. Neuro. Oncol. 15, 269-278.
49. Kataoka, H., and Sekiguchi, M. (1985). Molecular cloning and characterization of the alkB gene of Escherichia coli. Mol. Gen. Genet. 198, 263-269.
50. Kataoka, H., Yamamoto, Y., and Sekiguchi, M. (1983). A new gene (alkB) of Escherichia coli that controls sensitivity to methyl methane sulfonate. J. Bacteriol. 153, 1301-1307.
51. Katoh, K., and Toh, H. (2010). Parallelization of the MAFFT multiple sequence alignment program. Bioinformatics 26, 1899-1900.
52. Kirino, Y., Yasukawa, T., Ohta, S., et al. (2004). Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease. Proc. Natl Acad. Sci. USA 101, 15070-15075.
53. Klungland, A., and Dahl, J.A. (2014). DynamicRNA modifications in disease. Curr. Opin. Genet. Dev. 26C, 47-52.
54. Koike, K., Ueda, Y., Hase, H., et al. (2012). anti-tumor effect of AlkB homolog 3 knockdown in hormone-independent prostate cancer cells. Curr. Cancer Drug Targets 12, 847-856.
55. Koivisto, P., Duncan, T., Lindahl, T., et al. (2003). Minimal methylated substrate and extended substrate range of Escherichia coli AlkB protein, a 1-methyladenine-DNA dioxygenase. J. Biol. Chem. 278, 44348-44354.
56. Koivisto, P., Robins, P., Lindahl, T., et al. (2004). Demethylation of 3-methylthymine in DNA by bacterial and human DNA dioxygenases. J. Biol. Chem. 279, 40470-40474.
57. Korvald, H.,MolstadMoe,A.M.,Cederkvist, F.H.,etal. (2011).Schizosaccharomyces pombe Ofd2 is a nuclear 2-oxoglutarate and iron dependent dioxygenase interacting with histones. PLoS One 6, e25188.
58. Kurowski, M.A., Bhagwat, A.S., Papaj, G., et al. (2003). Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB. BMC Genomics 4, 48.
59. Lando, D., Balmer, J., Laue, E.D., et al. (2012). The S. pombe histone H2A dioxygenase Ofd2 regulates gene expression during hypoxia. PLoS One 7, e29765.
60. Lee, D.H., Jin, S.G., Cai, S., et al. (2005). Repair of methylationdamageinDNAand RNA by mammalian AlkB homologues. J. Biol. Chem. 280, 39448-39459.
61. Li, M.M., Nilsen, A., Shi, Y., et al. (2013). ALKBH4-dependent demethylation of actin regulates actomyosin dynamics. Nat. Commun. 4, 1832.
62. Lindahl, T. (1993). Instability and decay of the primary structure of DNA. Nature 362, 709-715.
63. Liu, J., Yue, Y., Han, D., et al. (2014).A METTL3-METTL14 complex mediatesmammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10, 93-95.
64. Loh, Y.H., Wu, Q., Chew, J.L., et al. (2006). The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat. Genet. 38, 431-440.
65. Loh, Y.H., Zhang,W., Chen, X., et al. (2007). Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev. 21, 2545-2557.
66. Meyer, K.D., and Jaffrey, S.R. (2014). The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat. Rev. Mol. Cell Biol. 15, 313-326.
67. Meyer, K.D., Saletore, Y., Zumbo, P., et al. (2012). Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149, 1635-1646.
68. Muller, R., Misund, K., Holien, T., et al. (2013a). Targeting proliferating cell nuclear antigen and its protein interactions induces apoptosis in multiple myeloma cells. PLoS One 8, e70430.
69. Muller, T.A., Yu, K., Hausinger, R.P., et al. (2013b). ALKBH1 is dispensable for abasic site cleavage during base excision repair and class switch recombination. PLoS One 8, e67403.
70. Nakao, S., Mabuchi, M., Shimizu, T., et al. (2014). Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg. Med. Chem. Lett. 24, 1071-1074.
71. Nay, S.L., Lee, D.H., Bates, S.E., et al. (2012). Alkbh2 protects against lethality and mutation in primary mouse embryonic fibroblasts. DNA Repair (Amst) 11, 502-510.
72. Neta, G., Brenner, A.V., Sturgis, E.M., et al. (2011). Common genetic variants related to genomic integrity and risk of papillary thyroid cancer. Carcinogenesis 32, 1231-1237.
73. Nichols, J.L., and Welder, L. (1981). A modified nucleotide in the poly(A) tract of maize RNA. Biochim. Biophys. Acta 652, 99-108.
74. Nilsen, A., Fusser, M., Greggains, G., et al. (2014). ALKBH4 depletion in mice leads to spermatogenic defects. PLoS One 9, e105113.
75. Nordstrand, L.M., Svard, J., Larsen, E., et al. (2010). Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects. PLoS One 5, e13827.
76. Ougland, R., Zhang, C.M., Liiv, A., et al. (2004). AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. Mol. Cell 16, 107-116.
77. Ougland, R., Lando, D., Jonson, I., et al. (2012). ALKBH1 is a histone H2A dioxygenase involved in neural differentiation. Stem Cells 30, 2672-2682.
78. Pan, Z., Sikandar, S., Witherspoon, M., et al. (2008). Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice. Dev. Dyn. 237, 316-327.
79. Ping, X.L., Sun, B.F., Wang, L., et al. (2014). Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 24, 177-189.
80. Ringvoll, J., Nordstrand, L.M., Vagbo, C.B., et al. (2006). Repair deficient mice reveal mABH2 as the primary oxidative demethylase for repairing 1meA and 3meC lesions in DNA. EMBO J. 25, 2189-2198.
81. Ringvoll, J., Moen, M.N., Nordstrand, L.M., et al. (2008). AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Res. 68, 4142-4149.
82. Robertson, A.B., Klungland, A., Rognes, T., et al. (2009). DNA repair in mammalian cells: base excision repair: the long and short of it. Cell. Mol. Life Sci. 66, 981-993.
83. Robinson, D.N., and Spudich, J.A. (2000). Towards a molecular understanding of cytokinesis. Trends Cell Biol. 10, 228-237.
84. Rydberg, B., and 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, 211-216.
85. Saitou, N., and Nei, M. (1987). The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406-425.
86. Saneyoshi, M., Harada, F., and Nishimura, S. (1969). Isolation and characterization of N6-methyladenosine from Escherichia coli valine transfer RNA. Biochim. Biophys. Acta 190, 264-273.
87. Schibler, U., Kelley, D.E., and Perry, R.P. (1977). Comparison of methylated sequences in messenger RNA and heterogeneous nuclear RNA from mouse L cells. J. Mol. Biol. 115, 695-714.
88. Schofield, C.J., and Zhang, Z. (1999). Structural and mechanistic studies on 2-oxoglutarate-dependent oxygenases and related enzymes. Curr. Opin. Struct. Biol. 9, 722-731.
89. Scott, L.J., Mohlke, K.L., Bonnycastle, L.L., et al. (2007). A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316, 1341-1345.
90. Scuteri, A., Sanna, S., Chen,W.M., et al. (2007). Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 3, e115.
91. Sedgwick, B., Bates, P.A., Paik, J., et al. (2007). Repair of alkylated DNA: recent advances. DNA Repair (Amst) 6, 429-442.
92. Shimada, K., Fujii, T., Tsujikawa, K., et al. (2012). ALKBH3 contributes to survival and angiogenesis of human urothelial carcinoma cells through NADPH oxidase and tweak/Fn14/VEGF signals. Clin. Cancer Res. 18, 5247-5255.
93. Smemo, S., Tena, J.J., Kim, K.H., et al. (2014). Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507, 371-375.
94. Solberg, A., Robertson, A.B., Aronsen, J.M., et al. (2013). Deletion of mouse Alkbh7 leads to obesity. J. Mol. Cell Biol. 5, 194-203.
95. Songe-Moller, L., van den Born, E., Leihne, V., et al. (2010). Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding. Mol. Cell. Biol. 30, 1814-1827.
96. Sundheim, O., Vagbo, C.B., Bjoras, M., et al. (2006). Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage.EMBO J. 25, 3389-3397.
97. Suzuki, T., Suzuki, T., Wada, T., et al. (2002). Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases. EMBO J. 21, 6581-6589.
98. Tatusova, T., Ciufo, S., Fedorov, B., et al. (2014). RefSeq microbialgenomes database: new representation and annotation strategy. Nucleic Acids Res. 42, D553-D559.
99. 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, 700-706.
100. Thalhammer, A., Bencokova, Z., Poole, R., et al. (2011). Human AlkB homologue 5 is a nuclear 2-oxoglutarate dependent oxygenase and a direct target of hypoxia-inducible factor 1a (HIF-1a). PLoS One 6, e16210.
101. Trewick, S.C., Henshaw, T.F., Hausinger, R.P., et al. (2002). Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature 419, 174-178.
102. Tsujikawa, K., Koike, K., Kitae, K., et al. (2007). Expression and sub-cellular localization of human ABH family molecules. J. Cell. Mol. Med. 11, 1105-1116.
103. Tsukada, Y., Fang, J., Erdjument-Bromage, H., et al. (2006). Histone demethylation by a family of JmjC domain-containing proteins. Nature 439, 811-816.
104. Tuck, M.T. (1992). The formation of internal 6-methyladenine residues in eukaryotic messenger RNA. Int. J. Biochem. 24, 379-386.
105. Vagbo, C.B., Svaasand, E.K., Aas, P.A., et al. (2013). Methylation damage to RNA induced in vivo in Escherichia coli is repaired by endogenous AlkB as part of the adaptive response. DNA Repair (Amst) 12, 188-195.
106. van den Born, E., Omelchenko, M.V., Bekkelund, A., et al. (2008). Viral AlkB proteins repair RNA damage by oxidative demethylation. Nucleic Acids Res. 36, 5451-5461.
107. van den Born, E., Vagbo, C.B., Songe-Moller, L., et al. (2011). ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA. Nat. Commun. 2, 172.
108. Wang, G., He, Q., Feng, C., et al. (2014a). The atomic resolution structure of human AlkB homolog 7 (ALKBH7), a key protein for programmed necrosis and fat metabolism. J. Biol. Chem. 289, 27924-27936.
109. Wang, Y., Li, Y., Toth, J.I., et al. (2014b).N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 16, 191-198.
110. Waterhouse, A.M., Procter, J.B., Martin, D.M., et al. (2009). Jalview Version 2 - a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189-1191.
111. Wei, C.M., Gershowitz, A., and Moss, B. (1976). 5′-Terminal and internal methylated nucleotide sequences in HeLa cell mRNA. Biochemistry (Mosc) 15, 397-401.
112. Wei, Y.F., Carter, K.C., Wang, R.P., et al. (1996). Molecular cloning and functional analysis of a human cDNA encoding an Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair. Nucleic Acids Res. 24, 931-937.
113. Wei, F.Y., Suzuki, T.,Watanabe, S., et al. (2011). Deficit of tRNA(Lys) modification by Cdkal1 causes the development of type 2 diabetes in mice. J. Clin. Invest. 121, 3598-3608.
114. Wood, R.D. (1997). Nucleotide excision repair in mammalian cells. J. Biol. Chem. 272, 23465-23468.
115. Wu, Q., Saunders, R.A., Szkudlarek-Mikho, M., et al. (2010). The obesityassociated Fto gene is a transcriptional coactivator. Biochem. Biophys. Res. Commun. 401, 390-395.
116. Wu, S.S., Xu,W., Liu, S., et al. (2011). Down-regulation of ALKBH2 increases cisplatin sensitivity in H1299 lung cancer cells. Acta Pharmacol. Sin. 32, 393-398.
117. Yamato, I., Sho, M., Shimada, K., et al. (2012). PCA-1/ALKBH3 contributes to pancreatic cancer by supporting apoptotic resistance and angiogenesis. Cancer Res. 72, 4829-4839.
118. Yang, C.G., Yi, C., Duguid, E.M., et al. (2008). Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature 452, 961-965.
119. Yi, C., Chen, B., Qi, B., et al. (2012). Duplex interrogation by a direct DNA repair protein in search of base damage. Nat. Struct. Mol. Biol. 19, 671-676.
120. Yu, B., and Hunt, J.F. (2009). Enzymological and structural studies of the mechanism of promiscuous substrate recognition by the oxidative DNA repair enzyme AlkB. Proc. Natl Acad. Sci. USA 106, 14315-14320.
121. Zdzalik, D., Vagbo, C.B., Kirpekar, F., et al. (2014). Protozoan ALKBH8 oxygenases display both DNA repair and tRNA modification activities. PLoS One 9, e98729.
122. Zheng, G., Dahl, J.A., Niu, Y., et al. (2013). ALKBH5 is amammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49, 18-29.
123. Zhou, Q., Chipperfield, H., Melton, D.A., et al. (2007). A gene regulatory network in mouse embryonic stem cells. Proc. Natl Acad. Sci. USA 104, 16438-16443.
124. Zhu, C., and Yi, C. (2014). Switching demethylation activities between AlkB family RNA/DNA demethylases through exchange of active-site residues. Angew. Chem. Int. Ed. Engl. 53, 3659-3662.