| General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction |
Basic Information | |
|---|---|
Gene ID | 29128 |
Name | UHRF1 |
Synonymous | ubiquitin-like with PHD and ring finger domains 1;UHRF1;ubiquitin-like with PHD and ring finger domains 1 |
Definition | E3 ubiquitin-protein ligase UHRF1|RING finger protein 106|inverted CCAAT box-binding protein of 90 kDa|nuclear phosphoprotein 95|nuclear protein 95|nuclear zinc finger protein Np95|transcription factor ICBP90|ubiquitin-like PHD and RING finger domain-cont |
Position | 19p13.3 |
Gene type | protein-coding |
Title | Abstract |
| UHRF1 is an oncogene that promotes DNA hypomethylation. | Dyskerin is a conserved, nucleolar RNA-binding protein implicated in an increasing array of fundamental cellular processes. Germline mutation in the dyskerin gene (DKC1) is the cause of X-linked dyskeratosis congenita (DC). Conversely, wild-type dyskerin is overexpressed in sporadic cancers, and high-levels may be associated with poor prognosis. It was previously reported that acute loss of dyskerin function via siRNA-mediated depletion slowed the proliferation of transformed cell lines. However, the mechanisms remained unclear. Using human U2OS osteosarcoma cells, we show that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. senescence can render cells resistant to apoptosis. Conversely, chromatin relaxation can reverse the repressive effects of senescence-associated heterochromatinization on apoptosis. To this end, genotoxic stress-induced apoptosis was suppressed in dyskerin-depleted cells. In contrast, agents that induce chromatin relaxation, including histone deacetylase inhibitors and the DNA intercalator chloroquine, sensitized dyskerin-depleted cells to apoptosis. Dyskerin is a core component of the telomerase complex and plays an important role in telomere homeostasis. Defective telomere maintenance resulting in premature senescence is thought to primarily underlie the pathogenesis of X-linked DC. Since U2OS cells are telomerase-negative, this leads us to conclude that loss of dyskerin function can also induce cellular senescence via mechanisms independent of telomere shortening. |