Compared to other NHEJ factors, DNA-PK protein and RNA levels are markedly increased in all higher primates, but not in prosimians or other mammals.
DNA Repair (Amst)
; 142: 103737, 2024 Oct.
Article
in En
| MEDLINE
| ID: mdl-39128395
ABSTRACT
The DNA dependent protein kinase (DNA-PK) initiates non-homologous recombination (NHEJ), the predominate DNA double-strand break (DSBR) pathway in higher vertebrates. It has been known for decades that the enzymatic activity of DNA-PK [that requires its three component polypeptides, Ku70, Ku80 (that comprise the DNA-end binding Ku heterodimer), and the catalytic subunit (DNA-PKcs)] is present in humans at 10-50 times the level observed in other mammals. Here, we show that the high level of DNA-PKcs protein expression appears evolutionarily in mammals between prosimians and higher primates. Moreover, the RNAs encoding the three component polypeptides of DNA-PK are present at similarly high levels in hominids, new-, and old-world monkeys, but expression of these RNAs in prosimians is â¼5-50 fold less, analogous to the levels observed in other non-primate species. This is reminiscent of the appearance of Alu repeats in primate genomes -- abundant in higher primates, but present at much lower density in prosimians. Alu repeats are well-known for their capacity to promote non-allelic homologous recombination (NAHR) a process known to be inhibited by DNA-PK. Nanopore sequence analyses of cultured cells proficient or deficient in DNA-PK revealed an increase of inter-chromosomal translocations caused by NAHR. Although the high levels of DNA-PK in primates may have many functions, we posit that high levels of DNA-PK may function to restrain deleterious NAHR events between Alu elements.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Primates
/
DNA-Activated Protein Kinase
/
DNA End-Joining Repair
Limits:
Animals
/
Humans
Language:
En
Journal:
DNA Repair (Amst)
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2024
Document type:
Article
Country of publication: