7L4V

C-terminal bZIP domain of human C/EBPbeta Bound to DNA with Consensus Recognition with GT Mismatch

Summary for 7L4V

• Entry DOI: 10.2210/pdb7l4v/pdb
• Descriptor: CCAAT/enhancer-binding protein beta, DNA Strand 1, DNA Strand 2, ... (5 entities in total)
• Functional Keywords: bzip transciption factor dna methylation cpa methylation protein-dna complex, transcription, transcription-dna complex, g-t dna mismatch, transcription/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 28771.25

Authors

Horton, J.R.,Cheng, X. (deposition date: 2020-12-21, release date: 2021-11-03, Last modification date: 2023-10-18)

Primary citation

Yang, J.,Horton, J.R.,Akdemir, K.C.,Li, J.,Huang, Y.,Kumar, J.,Blumenthal, R.M.,Zhang, X.,Cheng, X.
Preferential CEBP binding to T:G mismatches and increased C-to-T human somatic mutations.
Nucleic Acids Res., 49:5084-5094, 2021

PubMed Abstract: DNA cytosine methylation in mammals modulates gene expression and chromatin accessibility. It also impacts mutation rates, via spontaneous oxidative deamination of 5-methylcytosine (5mC) to thymine. In most cases the resulting T:G mismatches are repaired, following T excision by one of the thymine DNA glycosylases, TDG or MBD4. We found that C-to-T mutations are enriched in the binding sites of CCAAT/enhancer binding proteins (CEBP). Within a CEBP site, the presence of a T:G mismatch increased CEBPβ binding affinity by a factor of >60 relative to the normal C:G base pair. This enhanced binding to a mismatch inhibits its repair by both TDG and MBD4 in vitro. Furthermore, repair of the deamination product of unmethylated cytosine, which yields a U:G DNA mismatch that is normally repaired via uracil DNA glycosylase, is also inhibited by CEBPβ binding. Passage of a replication fork over either a T:G or U:G mismatch, before repair can occur, results in a C-to-T mutation in one of the daughter duplexes. Our study thus provides a plausible mechanism for accumulation of C-to-T human somatic mutations.

PubMed: 33877329
DOI: 10.1093/nar/gkab276

Experimental method

X-RAY DIFFRACTION (1.75 Å)