Thymine DNA glycosylase combines sliding, hopping, and nucleosome interactions to efficiently search for 5-formylcytosine.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
19
04
2024
accepted:
10
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Base excision repair is the main pathway involved in active DNA demethylation. 5-formylcytosine and 5-carboxylcytosine, two oxidized moieties of methylated cytosine, are recognized and removed by thymine DNA glycosylase (TDG) to generate an abasic site. Using single molecule fluorescence experiments, we study TDG in the presence and absence of 5-formylcytosine. TDG exhibits multiple modes of linear diffusion, including hopping and sliding, in search of base modifications. TDG active site variants and truncated N-terminus, reveals these variants alter base modification search and recognition mechanism of TDG. On DNA containing an undamaged nucleosome, TDG is found to either bypass, colocalize with, or encounter but not bypass the nucleosome. Truncating the N-terminus reduces the number of interactions with the nucleosome. Our findings provide mechanistic insights into how TDG searches for modified DNA bases in chromatin.
Identifiants
pubmed: 39455577
doi: 10.1038/s41467-024-53497-7
pii: 10.1038/s41467-024-53497-7
doi:
Substances chimiques
Thymine DNA Glycosylase
EC 3.2.2.-
5-formylcytosine
0
Cytosine
8J337D1HZY
Nucleosomes
0
DNA
9007-49-2
5-carboxylcytosine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9226Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)
ID : R35ES031638
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)
ID : F32ES034982
Organisme : U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD)
ID : S10OD032158-01A1
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : T32GM088119
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R35-GM136225
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R35GM128562
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : F32GM140718
Informations de copyright
© 2024. The Author(s).
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