scholarly journals Thymine DNA glycosylase recognizes the geometry alteration of minor grooves induced by 5-formylcytosine and 5-carboxylcytosine

2019 ◽  
Vol 10 (31) ◽  
pp. 7407-7417 ◽  
Author(s):  
Tianran Fu ◽  
Liping Liu ◽  
Qing-Lin Yang ◽  
Yuxin Wang ◽  
Pan Xu ◽  
...  
Keyword(s):  
Dna Demethylation ◽  
Dna Glycosylase ◽  
Thymine Dna Glycosylase

Thymine DNA glycosylase (TDG) recognizes the geometry alteration of DNA minor grooves induced by 5-formylcytosine (5fC) in DNA demethylation pathways.

scholarly journals Thymine DNA Glycosylase Can Rapidly Excise 5-Formylcytosine and 5-Carboxylcytosine

2011 ◽  
Vol 286 (41) ◽  
pp. 35334-35338 ◽  
Author(s):  
Atanu Maiti ◽  
Alexander C. Drohat
Keyword(s):  
Embryonic Development ◽  
Catalytic Mechanism ◽  
Excision Repair ◽  
Dna Demethylation ◽  
Oxidation Products ◽  
Dna Glycosylase ◽  
Thymine Dna Glycosylase ◽  
Active Demethylation ◽  
Active Dna Demethylation ◽  
Base Excision

Thymine DNA glycosylase (TDG) excises T from G·T mispairs and is thought to initiate base excision repair (BER) of deaminated 5-methylcytosine (mC). Recent studies show that TDG, including its glycosylase activity, is essential for active DNA demethylation and embryonic development. These and other findings suggest that active demethylation could involve mC deamination by a deaminase, giving a G·T mispair followed by TDG-initiated BER. An alternative proposal is that demethylation could involve iterative oxidation of mC to 5-hydroxymethylcytosine (hmC) and then to 5-formylcytosine (fC) and 5-carboxylcytosine (caC), mediated by a Tet (ten eleven translocation) enzyme, with conversion of caC to C by a putative decarboxylase. Our previous studies suggest that TDG could excise fC and caC from DNA, which could provide another potential demethylation mechanism. We show here that TDG rapidly removes fC, with higher activity than for G·T mispairs, and has substantial caC excision activity, yet it cannot remove hmC. TDG excision of fC and caC, oxidation products of mC, is consistent with its strong specificity for excising bases from a CpG context. Our findings reveal a remarkable new aspect of specificity for TDG, inform its catalytic mechanism, and suggest that TDG could protect against fC-induced mutagenesis. The results also suggest a new potential mechanism for active DNA demethylation, involving TDG excision of Tet-produced fC (or caC) and subsequent BER. Such a mechanism obviates the need for a decarboxylase and is consistent with findings that TDG glycosylase activity is essential for active demethylation and embryonic development, as are mechanisms involving TDG excision of deaminated mC or hmC.

scholarly journals Reversible chromatin condensation by the DNA repair and demethylation factor thymine DNA glycosylase

2021 ◽  
Author(s):  
Charles E Deckard ◽  
Jonathan T Sczepanski
Keyword(s):  
Dna Repair ◽  
Chromatin Condensation ◽  
Methylation Status ◽  
Dna Demethylation ◽  
Dna Glycosylase ◽  
New Paradigm ◽  
Thymine Dna Glycosylase ◽  
Terminal Domain ◽  
Self Association ◽  
Nucleosome Arrays

Abstract Chromatin structures (and modulators thereof) play a central role in genome organization and function. Herein, we report that thymine DNA glycosylase (TDG), an essential enzyme involved in DNA repair and demethylation, has the capacity to alter chromatin structure directly through its physical interactions with DNA. Using chemically defined nucleosome arrays, we demonstrate that TDG induces decompaction of individual chromatin fibers upon binding and promotes self-association of nucleosome arrays into higher-order oligomeric structures (i.e. condensation). Chromatin condensation is mediated by TDG’s disordered polycationic N-terminal domain, whereas its C-terminal domain antagonizes this process. Furthermore, we demonstrate that TDG-mediated chromatin condensation is reversible by growth arrest and DNA damage 45 alpha (GADD45a), implying that TDG cooperates with its binding partners to dynamically control chromatin architecture. Finally, we show that chromatin condensation by TDG is sensitive to the methylation status of the underlying DNA. This new paradigm for TDG has specific implications for associated processes, such as DNA repair, DNA demethylation, and transcription, and general implications for the role of DNA modification ‘readers’ in controlling chromatin organization.

scholarly journals Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair

Cell ◽  
2011 ◽  
Vol 146 (1) ◽  
pp. 67-79 ◽  
Author(s):  
Salvatore Cortellino ◽  
Jinfei Xu ◽  
Mara Sannai ◽  
Robert Moore ◽  
Elena Caretti ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Dna Demethylation ◽  
Dna Glycosylase ◽  
Thymine Dna Glycosylase ◽  
Active Dna Demethylation ◽  
Base Excision

scholarly journals ROS1 5-methylcytosine DNA glycosylase is a slow-turnover catalyst that initiates DNA demethylation in a distributive fashion

2009 ◽  
Vol 37 (13) ◽  
pp. 4264-4274 ◽  
Author(s):  
María Isabel Ponferrada-Marín ◽  
Teresa Roldán-Arjona ◽  
Rafael R. Ariza
Keyword(s):  
Dna Demethylation ◽  
Dna Glycosylase ◽  
Slow Turnover

scholarly journals SUMO-1 regulates the conformational dynamics of Thymine-DNA Glycosylase regulatory domain and competes with its DNA binding activity

2011 ◽  
Vol 12 (1) ◽  
pp. 4 ◽  
Author(s):  
Caroline Smet-Nocca ◽  
Jean-Michel Wieruszeski ◽  
Hélène Léger ◽  
Sebastian Eilebrecht ◽  
Arndt Benecke
Keyword(s):  
Dna Binding ◽  
Conformational Dynamics ◽  
Binding Activity ◽  
Dna Glycosylase ◽  
Regulatory Domain ◽  
Thymine Dna Glycosylase ◽  
Dna Binding Activity
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