Publications by authors named "Olga Kotljarova"

2 Publications

  • Page 1 of 1

Synthesis of (R)-Configured 2'-Fluorinated mC, hmC, fC, and caC Phosphoramidites and Oligonucleotides.

Org Lett 2016 09 19;18(17):4368-71. Epub 2016 Aug 19.

Center for Integrated Protein Science, Department of Chemistry, Ludwig-Maximilians-Universität München , Butenandtstraße 5-13, 81377 Munich, Germany.

Investigation of the function of the new epigenetic bases requires the development of stabilized analogues that are stable during base excision repair (BER). Here we report the synthesis of 2'-(R)-fluorinated versions of the phosphoramidites of 5-methylcytosine (mC), 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxycytosine (caC). For oligonucleotides containing 2'-(R)-F-fdC, we show that these compounds cannot be cleaved by the main BER enzyme thymine-DNA glycosylase (TDG).
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http://dx.doi.org/10.1021/acs.orglett.6b02110DOI Listing
September 2016

Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA.

Nat Chem Biol 2014 Jul 18;10(7):574-81. Epub 2014 May 18.

Center for Integrated Protein Science at the Department of Chemistry, Ludwig-Maximilians-Universität München, München, Germany.

Ten eleven translocation (Tet) enzymes oxidize the epigenetically important DNA base 5-methylcytosine (mC) stepwise to 5-hydroxymethylcytosine (hmC), 5-formylcytosine and 5-carboxycytosine. It is currently unknown whether Tet-induced oxidation is limited to cytosine-derived nucleobases or whether other nucleobases are oxidized as well. We synthesized isotopologs of all major oxidized pyrimidine and purine bases and performed quantitative MS to show that Tet-induced oxidation is not limited to mC but that thymine is also a substrate that gives 5-hydroxymethyluracil (hmU) in mouse embryonic stem cells (mESCs). Using MS-based isotope tracing, we show that deamination of hmC does not contribute to the steady-state levels of hmU in mESCs. Protein pull-down experiments in combination with peptide tracing identifies hmU as a base that influences binding of chromatin remodeling proteins and transcription factors, suggesting that hmU has a specific function in stem cells besides triggering DNA repair.
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http://dx.doi.org/10.1038/nchembio.1532DOI Listing
July 2014