The enigmatic thymine DNA glycosylase

Cortázar, Daniel; Kunz, Christophe; Saito, Yûsuke; Steinacher, Roland; Schär, Primo

doi:10.1016/j.dnarep.2006.10.013

Cited by 175 publications

(198 citation statements)

References 106 publications

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“…In general agreement with such an idea, the PIP degron is only present in animals that exhibit cytosine DNA methylation (Fig. 1A) (59). CRL4 Cdt2 -dependent TDG destruction might be important to regulate DNA methylation levels during development.…”

Section: Discussionsupporting

confidence: 59%

Thymine DNA Glycosylase Is a CRL4Cdt2 Substrate

Slenn

Morris

Havens

et al. 2014

Journal of Biological Chemistry

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Background: E3 ubiquitin ligases facilitate destruction of other proteins. Results: In frog egg extract, the DNA repair factor thymine DNA glycosylase (TDG) was destroyed during DNA replication and repair, dependent on the E3 ubiquitin ligase CRL4 Cdt2 . Conclusion: TDG is a novel target of CRL4 Cdt2 . Significance: We identified a novel form of TDG regulation that informs how cells regulate S phase and epigenetic inheritance.

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Section: Discussionsupporting

confidence: 59%

Thymine DNA Glycosylase Is a CRL4Cdt2 Substrate

Slenn

Morris

Havens

et al. 2014

Journal of Biological Chemistry

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“…While DNA glycosylases are best known for repair of damaged and mismatched bases, recent work indicates that they also play roles in transcriptional regulation. The mammalian DNA glycosylase thymine DNA glycosylase (TDG) acts as a transcriptional co-activator, when bound to CREB-binding protein (CBP) and p300 (Tini et al 2002), to enhance CBP-activated transcription in cell culture (Cortazar et al 2007). It also acts as a transcriptional corepressor when bound to thyroid transcription factor-1 (TTF1) to repress TTF1-activated transcription in cell culture (Cortazar et al 2007;Kovtun and McMurray 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The mammalian DNA glycosylase thymine DNA glycosylase (TDG) acts as a transcriptional co-activator, when bound to CREB-binding protein (CBP) and p300 (Tini et al 2002), to enhance CBP-activated transcription in cell culture (Cortazar et al 2007). It also acts as a transcriptional corepressor when bound to thyroid transcription factor-1 (TTF1) to repress TTF1-activated transcription in cell culture (Cortazar et al 2007;Kovtun and McMurray 2007). The Arabidopsis DNA glycosylase DEMETER is required to activate expression of the maternal MEDEA allele, an imprinted maternal gene essential for viability (Choi et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…DNA glycosylases initiate an evolutionarily conserved base excision repair pathway by excising mismatched or altered bases that result from processes including oxidation, deamination, alkylation, and methylation (Dizdaroglu 2005). In addition, DNA glycosylases have been shown to act as transcriptional regulators (Choi et al 2002;Cortazar et al 2007).…”

Section: ; Muller Et Al 2005) Ep(x)1503 a Uas-containing Transmentioning

confidence: 99%

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A Screen for Modifiers of Notch Signaling Uncovers Amun, a Protein With a Critical Role in Sensory Organ Development

et al. 2009

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Notch signaling is an evolutionarily conserved pathway essential for many cell fate specification events during metazoan development. We conducted a large-scale transposon-based screen in the developing Drosophila eye to identify genes involved in Notch signaling. We screened 10,447 transposon lines from the Exelixis collection for modifiers of cell fate alterations caused by overexpression of the Notch ligand Delta and identified 170 distinct modifier lines that may affect up to 274 genes. These include genes known to function in Notch signaling, as well as a large group of characterized and uncharacterized genes that have not been implicated in Notch pathway function. We further analyze a gene that we have named Amun and show that it encodes a protein that localizes to the nucleus and contains a putative DNA glycosylase domain. Genetic and molecular analyses of Amun show that altered levels of Amun function interfere with cell fate specification during eye and sensory organ development. Overexpression of Amun decreases expression of the proneural transcription factor Achaete, and sensory organ loss caused by Amun overexpression can be rescued by coexpression of Achaete. Taken together, our data suggest that Amun acts as a transcriptional regulator that can affect cell fate specification by controlling Achaete levels.

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“…TDG hydrolyzes the carbon-nitrogen bond between the sugarphosphate backbone of DNA and the mispaired thymine, thus removing the thymine moiety from G:T mismatches and creating an abasic site which is repaired by subsequent enzymatic steps in this BER pathway. 5,6 The enzyme methyl-CpG-binding the protein remains "mutant-like"), this cell line has been previously used as a model to identify p53-regulated genes in an ESCC background. 25,26 Figure 1A shows a 4-fold higher level of TDG mRNA in TE-1 cells at 32°C, than at 37°C.…”

Section: Transcriptional Regulation Of Thymine Dna Glycosylase (Tdg) mentioning

confidence: 99%