| RRC ID |
76129
|
| 著者 |
Bujarrabal-Dueso A, Sendtner G, Meyer DH, Chatzinikolaou G, Stratigi K, Garinis GA, Schumacher B.
|
| タイトル |
The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities.
|
| ジャーナル |
Nat Struct Mol Biol
|
| Abstract |
The DNA-repair capacity in somatic cells is limited compared with that in germ cells. It has remained unknown whether not only lesion-type-specific, but overall repair capacities could be improved. Here we show that the DREAM repressor complex curbs the DNA-repair capacities in somatic tissues of Caenorhabditis elegans. Mutations in the DREAM complex induce germline-like expression patterns of multiple mechanisms of DNA repair in the soma. Consequently, DREAM mutants confer resistance to a wide range of DNA-damage types during development and aging. Similarly, inhibition of the DREAM complex in human cells boosts DNA-repair gene expression and resistance to distinct DNA-damage types. DREAM inhibition leads to decreased DNA damage and prevents photoreceptor loss in progeroid Ercc1-/- mice. We show that the DREAM complex transcriptionally represses essentially all DNA-repair systems and thus operates as a highly conserved master regulator of the somatic limitation of DNA-repair capacities.
|
| 巻・号 |
30(4)
|
| ページ |
475-488
|
| 公開日 |
2023-4-1
|
| DOI |
10.1038/s41594-023-00942-8
|
| PII |
10.1038/s41594-023-00942-8
|
| PMID |
36959262
|
| PMC |
PMC10113156
|
| MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
DNA / metabolism
DNA Damage
DNA Repair
Germ Cells / metabolism
Humans
Mice
|
| リソース情報 |
| 線虫 |
tm3886
tm1489
tm4539
tm1524
tm1145 |
