MCM3
DNA replication licensing factor MCM3 (EC 3.6.4.12) (DNA polymerase alpha holoenzyme-associated protein P1) (P1-MCM3) (RLF subunit beta) (p102)
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Cellular aging is characterized by the loss of DNA replication capability and is mainly brought about by various changes in chromatin structure. Here, we examined changes in MCM2-7 proteins, which act as a replicative DNA helicase, during aging of human WI38 fibroblasts at the single-cell level. We used nuclear accumulation of p21 as a marker of senescent cells, and examined changes in MCM2-7 by western blot analysis. First, we found that senescent cells are enriched for cells with a DNA content higher than 4N. Second, the levels of MCM2, MCM3, MCM4 and MCM6 proteins decreased in senescent cells. Third, cytoplasmic localization of MCM2 and MCM7 was observed in senescent cells, from an analysis of MCM2-7 except for MCM5. Consistent with this finding, fragmented MCM2 was predominant in these cells. These age-dependent changes in MCM2-7, a protein complex that directly affects cellular DNA replication, may play a critical role in cellular senescence.
MeSH Terms
- Cell Cycle Proteins
- Cellular Senescence
- DNA Replication
- Gene Expression Regulation
- Humans
- Minichromosome Maintenance Complex Component 2
- Minichromosome Maintenance Complex Component 3
- Minichromosome Maintenance Complex Component 4
- Minichromosome Maintenance Complex Component 6
- Minichromosome Maintenance Complex Component 7
- Multiprotein Complexes
- Single-Cell Analysis
- p21-Activated Kinases
Keywords
- DNA content
- MCM2–7 proteins
- cellular aging
- cellular localization
- protein degradation
Minichromosome maintenance complex component 3, one of the minichromosome maintenance proteins, functions as a part of pre-replication complex to initiate DNA replication in eukaryotes. Minichromosome maintenance complex component 3 (MCM3) was mainly implied in cell proliferation and tumorigenesis. In addition, MCM3 might play an important role in neuronal apoptosis. However, the functions of MCM3 in central nervous system are still with limited acquaintance. In this study, we performed a traumatic brain injury (TBI) model in adult rats. Western blot and immunohistochemistry staining showed up-regulation of MCM3 in the peritrauma brain cortex. The expression patterns of active caspase-3 and Bax, Bcl-2 were parallel with that of MCM3. Immunofluorescent staining and terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling suggested that MCM3 was involved in neuronal apoptosis. In conclusion, our data indicated that MCM3 might play an important role in neuronal apoptosis following TBI. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against TBI.
MeSH Terms
- Aging
- Animals
- Apoptosis
- Brain Injuries, Traumatic
- Cerebral Cortex
- Minichromosome Maintenance Complex Component 3
- Neurons
- Rats, Sprague-Dawley
- Transcriptional Activation
- Up-Regulation
Keywords
- Active caspase-3
- BAX/Bcl-2
- MCM3
- Neuronal apoptosis
- TBI