A5009274061- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Pancreatic and Hepatic Oncology Research
- Pluripotent Stem Cells Research
- Cancer Research and Treatments
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
Universität Ulm
2020-2024
Klinik für Frauenheilkunde
2020
It is well-established that, through canonical functions in transcription and DNA repair, the tumor suppressor p53 plays a central role safeguarding cells from consequences of damage. Recent data retrieved stem demonstrated that also carries out non-canonical when interacting with translesion synthesis (TLS) polymerase iota (POLι) at replication forks. This protein complex triggers damage tolerance (DDT) mechanism controlling rate. Given levels trigger non-binary rheostat-like response to...
(ATM) is the most frequently mutated DNA damage response gene, involved in homologous recombination (HR), pancreatic ductal adenocarcinoma (PDAC).
Abstract Using human embryonic, adult and cancer stem cells/stem cell-like cells (SCs), we demonstrate that DNA replication speed differs in SCs their differentiated counterparts. While decelerate replication, synthesize faster accumulate damage. Notably, both phenotypes depend on p53 polymerase iota (POLι). By exploring protein interactions newly synthesized DNA, show promote complex formation of POLι at sites. Intriguingly, the translocase ZRANB3 is recruited to required for slow-down...
We have previously reported that p53 decelerates nascent DNA elongation in complex with the translesion synthesis (TLS) polymerase ι (POLι) which triggers a homology-directed damage tolerance (DDT) pathway to bypass obstacles during replication. Here, we demonstrate this DDT relies on multiple activities, can be disrupted by TP53 mutations including those frequently found cancer tissues. show p53-mediated depends its oligomerization domain (OD), while regulatory C-terminus is not involved....
The recently discovered p53-dependent DNA damage tolerance (DDT) pathway relies on its biochemical activities in DNA-binding, oligomerization, as well complex formation with the translesion synthesis (TLS) polymerase iota (POLι). These p53-POLι complexes slow down nascent for safe, homology-directed bypass of replication barriers. In this study, we demonstrate that alternative p53-isoforms p53β, p53γ, Δ40p53α, Δ133p53α, and Δ160p53α differentially affect p53-POLι-dependent DDT originally...
Introduction In many tumors the mutational make up is taken into account by using targeted therapies. However, in pancreatic ductal adenocarcinoma (PDAC) these approaches often failed leaving standard chemotherapies as only first-line options. One of most promising subtypes to be genomic unstable one, counting for >10 % all PDACs. ATM serine/threonine kinase (ATM) frequently mutated gene this subgroup. important DNA-damage response (DDR) via homologous recombination (HR). The PARP inhibitor...