Insights into DNA Damage in Regenerating Young and Aged Mouse Livers
نویسندگان
چکیده
Abstract Background The maintenance of genome stability is a key process to slow aging. One the mechanisms ensuring this correct coordination origins replication (ORI), resulting in successful transmission DNA. Previously, we mapped and compared ORI firing between young aged mice vivo, using regenerating liver mouse model. We confirmed decreased hepatocyte efficiency mice, known have impaired regeneration. proved be fully rescued when blocking mice's ATR serine/threonine-protein kinase, suggesting that DNA checkpoint actively mediates impairment upon damage detection. Aims To explore differences livers. Methods induce proliferation, were subjected partial hepatectomy (PH) sections harvested at different timepoints. Immunohistochemistry staining (IHC) used address proliferation damage, Ki67 serine 139 phosphorylated histone H2AX (g-H2AX) as markers, respectively. Results lack signal prior PH. takes off 24-28h post-PH reaches its peak 36-48h, which significantly lower mice. After 48h post-PH, hepatocytes’ basal level 120h post-PH. However, maintained low levels overtime. Next, kinetics Both groups present an increase g-H2AX PH, higher decreases hepatocytes after until disappearing post Aged maintain rates overtime Conclusions Our data suggests develop able resolved but remains livers, ultimately leading
منابع مشابه
DNA damage response and repair: insights into strategies for radiation sensitization of gliomas.
The incorporation of radiotherapy into multimodality treatment plans has led to significant improvements in glioma patient survival. However, local recurrence from glioma resistance to ionizing radiation remains a therapeutic challenge. The tumoricidal effect of radiation therapy is largely attributed to the induction of dsDNA breaks (DSBs). In the past decade, there have been tremendous stride...
متن کاملThe SOS response: recent insights into umuDC-dependent mutagenesis and DNA damage tolerance.
Be they prokaryotic or eukaryotic, organisms are exposed to a multitude of deoxyribonucleic acid (DNA) damaging agents ranging from ultraviolet (UV) light to fungal metabolites, like Aflatoxin B1. Furthermore, DNA damaging agents, such as reactive oxygen species, can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an or...
متن کاملNew Insights into p53 Signaling and Cancer Cell Response to DNA Damage: Implications for Cancer Therapy
Activation of the p53 signaling pathway by DNA-damaging agents was originally proposed to result either in cell cycle checkpoint activation to promote survival or in apoptotic cell death. This model provided the impetus for numerous studies focusing on the development of p53-based cancer therapies. According to recent evidence, however, most p53 wild-type human cell types respond to ionizing ra...
متن کاملNew insights into PARP inhibitors' effect on cell cycle and homology-directed DNA damage repair.
In preclinical and clinical studies, olaparib and veliparib are the most represented PARP inhibitors (PARPi), which mainly target homologous DNA damage repair pathway-deficient cancer cells. Their off-target effects are not fully understood, especially with regard to cell cycle and homology-directed DNA damage repair. Our objective was to comparatively evaluate olaparib and veliparib in this co...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: British Journal of Surgery
سال: 2023
ISSN: ['1365-2168', '0007-1323']
DOI: https://doi.org/10.1093/bjs/znad178.007