An Orc1/Cdc6 ortholog functions as a key regulator in the DNA damage response in Archaea.
Nucleic Acids Res
; 46(13): 6697-6711, 2018 07 27.
Article
in En
| MEDLINE
| ID: mdl-29878182
ABSTRACT
While bacteria and eukaryotes show distinct mechanisms of DNA damage response (DDR) regulation, investigation of ultraviolet (UV)-responsive expression in a few archaea did not yield any conclusive evidence for an archaeal DDR regulatory network. Nevertheless, expression of Orc1-2, an ortholog of the archaeal origin recognition complex 1/cell division control protein 6 (Orc1/Cdc6) superfamily proteins was strongly activated in Sulfolobus solfataricus and Sulfolobus acidocaldarius upon UV irradiation. Here, a series of experiments were conducted to investigate the possible functions of Orc1-2 in DNA damage repair in Sulfolobus islandicus. Study of DDR in Δorc1-2 revealed that Orc1-2 deficiency abolishes DNA damage-induced differential expression of a large number of genes and the mutant showed hypersensitivity to DNA damage treatment. Reporter gene and DNase I footprinting assays demonstrated that Orc1-2 interacts with a conserved hexanucleotide motif present in several DDR gene promoters and regulates their expression. Manipulation of orc1-2 expression by promoter substitution in this archaeon revealed that a high level of orc1-2 expression is essential but not sufficient to trigger DDR. Together, these results have placed Orc1-2 in the heart of the archaeal DDR regulation, and the resulting Orc1-2-centered regulatory circuit represents the first DDR network identified in Archaea, the third domain of life.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sulfolobus
/
Cell Cycle Proteins
/
Archaeal Proteins
/
DNA Repair
/
Origin Recognition Complex
Language:
En
Journal:
Nucleic Acids Res
Year:
2018
Type:
Article
Affiliation country:
China