DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro
5-Methylcytosine (5mC) in DNA CpG islands is an important epigenetic biomarker for mammalian gene regulation. It is oxidized to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the ten-eleven translocation (TET) family enzymes, which are -ketoglutarate (-KG)/F...
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| Format: | Article |
| Language: | English |
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Oxford University Press (OUP)
2020
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| Online Access: | https://hdl.handle.net/1721.1/125181 |
| _version_ | 1826189173612085248 |
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| author | Bian, Ke Lenz, Stefan A P Tang, Qi Chen, Fangyi Qi, Rui Jost, Marco Drennan, Catherine L Essigmann, John M Wetmore, Stacey D Li, Deyu |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Bian, Ke Lenz, Stefan A P Tang, Qi Chen, Fangyi Qi, Rui Jost, Marco Drennan, Catherine L Essigmann, John M Wetmore, Stacey D Li, Deyu |
| author_sort | Bian, Ke |
| collection | MIT |
| description | 5-Methylcytosine (5mC) in DNA CpG islands is an important epigenetic biomarker for mammalian gene regulation. It is oxidized to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the ten-eleven translocation (TET) family enzymes, which are -ketoglutarate (-KG)/Fe(II)-dependent dioxygenases. In this work, we demonstrate that the epigenetic marker 5mC is modified to 5hmC, 5fC, and 5caC in vitro by another class of -KG/Fe(II)-dependent proteins-the DNA repair enzymes in the AlkB family, which include ALKBH2, ALKBH3 in huamn and AlkB in Escherichia coli. Theoretical calculations indicate that these enzymes may bind 5mC in the synconformation, placing the methyl group comparable to 3-methylcytosine, the prototypic substrate of AlkB. This is the first demonstration of the AlkB proteins to oxidize a methyl group attached to carbon, instead of nitrogen, on a DNA base. These observations suggest a broader role in epigenetics for these DNA repair proteins. |
| first_indexed | 2024-09-23T08:10:39Z |
| format | Article |
| id | mit-1721.1/125181 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:10:39Z |
| publishDate | 2020 |
| publisher | Oxford University Press (OUP) |
| record_format | dspace |
| spelling | mit-1721.1/1251812022-09-23T11:25:38Z DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro Bian, Ke Lenz, Stefan A P Tang, Qi Chen, Fangyi Qi, Rui Jost, Marco Drennan, Catherine L Essigmann, John M Wetmore, Stacey D Li, Deyu Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Center for Environmental Health Sciences Massachusetts Institute of Technology. Department of Biological Engineering 5-Methylcytosine (5mC) in DNA CpG islands is an important epigenetic biomarker for mammalian gene regulation. It is oxidized to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the ten-eleven translocation (TET) family enzymes, which are -ketoglutarate (-KG)/Fe(II)-dependent dioxygenases. In this work, we demonstrate that the epigenetic marker 5mC is modified to 5hmC, 5fC, and 5caC in vitro by another class of -KG/Fe(II)-dependent proteins-the DNA repair enzymes in the AlkB family, which include ALKBH2, ALKBH3 in huamn and AlkB in Escherichia coli. Theoretical calculations indicate that these enzymes may bind 5mC in the synconformation, placing the methyl group comparable to 3-methylcytosine, the prototypic substrate of AlkB. This is the first demonstration of the AlkB proteins to oxidize a methyl group attached to carbon, instead of nitrogen, on a DNA base. These observations suggest a broader role in epigenetics for these DNA repair proteins. National Institute of General Medical Sciences (Grant P20 GM103430) National Cancer Institute (Grant P01 CA026731) National Cancer Institute (Grant R01 CA080024) National Cancer Institute (Grant P30 ES002109) 2020-05-12T15:37:29Z 2020-05-12T15:37:29Z 2019-05 2019-04 2019-12-03T19:26:51Z Article http://purl.org/eprint/type/JournalArticle 0305-1048 1362-4962 https://hdl.handle.net/1721.1/125181 Bian,Ke et al. "DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro." Nucleic Acids Research 47, 11 (June 2019): 5522–5529. ©2019 The Author(s). en http://dx.doi.org/10.1093/nar/gkz395 Nucleic Acids Research Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf Oxford University Press (OUP) Nucleic Acids Research |
| spellingShingle | Bian, Ke Lenz, Stefan A P Tang, Qi Chen, Fangyi Qi, Rui Jost, Marco Drennan, Catherine L Essigmann, John M Wetmore, Stacey D Li, Deyu DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro |
| title | DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro |
| title_full | DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro |
| title_fullStr | DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro |
| title_full_unstemmed | DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro |
| title_short | DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro |
| title_sort | dna repair enzymes alkbh2 alkbh3 and alkb oxidize 5 methylcytosine to 5 hydroxymethylcytosine 5 formylcytosine and 5 carboxylcytosine in vitro |
| url | https://hdl.handle.net/1721.1/125181 |
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