Human activation-induced deaminase lacks strong replicative strand bias or preference for cytosines in hairpin loops.
Nucleic Acids Res
; 50(9): 5145-5157, 2022 05 20.
Article
em En
| MEDLINE
| ID: mdl-35524550
ABSTRACT
Activation-induced deaminase (AID) is a DNA-cytosine deaminase that mediates maturation of antibodies through somatic hypermutation and class-switch recombination. While it causes mutations in immunoglobulin heavy and light chain genes and strand breaks in the switch regions of the immunoglobulin heavy chain gene, it largely avoids causing such damage in the rest of the genome. To help understand targeting by human AID, we expressed it in repair-deficient Escherichia coli and mapped the created uracils in the genomic DNA using uracil pull-down and sequencing, UPD-seq. We found that both AID and the human APOBEC3A preferentially target tRNA genes and transcription start sites, but do not show preference for highly transcribed genes. Unlike A3A, AID did not show a strong replicative strand bias or a preference for hairpin loops. Overlapping uracilation peaks between these enzymes contained binding sites for a protein, FIS, that helps create topological domains in the E. coli genome. To confirm whether these findings were relevant to B cells, we examined mutations from lymphoma and leukemia genomes within AID-preferred sequences. These mutations also lacked replicative strand bias or a hairpin loop preference. We propose here a model for how AID avoids causing mutations in the single-stranded DNA found within replication forks.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citidina Desaminase
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article