TDP2 is a regulator of estrogen-responsive oncogene expression.
NAR Cancer
; 6(2): zcae016, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38596431
ABSTRACT
With its ligand estrogen, the estrogen receptor (ER) initiates a global transcriptional program, promoting cell growth. This process involves topoisomerase 2 (TOP2), a key protein in resolving topological issues during transcription by cleaving a DNA duplex, passing another duplex through the break, and repairing the break. Recent studies revealed the involvement of various DNA repair proteins in the repair of TOP2-induced breaks, suggesting potential alternative repair pathways in cases where TOP2 is halted after cleavage. However, the contribution of these proteins in ER-induced transcriptional regulation remains unclear. We investigated the role of tyrosyl-DNA phosphodiesterase 2 (TDP2), an enzyme for the removal of halted TOP2 from the DNA ends, in the estrogen-induced transcriptome using both targeted and global transcription analyses. MYC activation by estrogen, a TOP2-dependent and transient event, became prolonged in the absence of TDP2 in both TDP2-deficient cells and mice. Bulk and single-cell RNA-seq analyses defined MYC and CCND1 as oncogenes whose estrogen response is tightly regulated by TDP2. These results suggest that TDP2 may inherently participate in the repair of estrogen-induced breaks at specific genomic loci, exerting precise control over oncogenic gene expression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
NAR Cancer
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Reino Unido