Changes in MCM2–7 proteins at senescence

Abstract

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.

Expression and Prognostic Value of MCM Family Genes in Osteosarcoma

“…It belongs to MADS box transcription factor family ( Pramila et al, 2002 ). The MCM2-7 form a heterohexameric complex that serves as a DNA duplicating helicase, which unwinds the DNA duplex template during DNA replication ( Fei and Xu, 2018 ; Suzuki et al, 2019 ). MCM8 and nine were reported to make up the CMG complex with Cdt1 and GINS.…”

Proteomes of primary skin fibroblasts from healthy individuals reveal altered cell responses across the life span

“…Similarly, the levels of MCM2-7 proteins were reported to decrease in replicative senescence (Suzuki et al, 2019). Notably, in both studies, MCM7 translocated to the cytosol with either increasing age or senescence, suggesting that besides steady-state levels, the exit from the nucleus could represent a full loss-of-function for MCM7.…”

“…It was previously reported that the levels of MCM2‐7 proteins were significantly lower in HDFs derived from healthy aged donors, and a role for MCM7 in proliferation was established by selective knockdown approaches (Dumit et al., 2014 ). Similarly, the levels of MCM2‐7 proteins were reported to decrease in replicative senescence (Suzuki et al., 2019 ). Notably, in both studies, MCM7 translocated to the cytosol with either increasing age or senescence, suggesting that besides steady‐state levels, the exit from the nucleus could represent a full loss‐of‐function for MCM7.…”

Juvenile zebrafish (Danio rerio) are able to recover from lordosis

“…There is evidence that transcription of mcm (for minichromosome maintenance) genes increases during the G1 phase of cell cycle. It is also known that limited levels of MCM proteins may disrupt cell proliferation through the arrest of cell cycle progression at G1 phase and may be associated to the status of cell senescence 29 , 30 . A decrease of cell proliferation process in the haemal tissue sampled in the recovered group (s-L/rec) is supported by the down expression of pcna gene ( p = 0.019) (supplementary data 1 ).…”