For the first time, pluripotent stem cells have been revealed to efficiently handle DNA replication pressures with unique mechanisms.

Recently, Zheng Ping's team at the Kunming Institute of Zoology of the Chinese Academy of Sciences made progress in the study of the stability of the genetic material of pluripotent stem cells, and the relevant research results were published online in Cell Research.
work for the first time reveals that pluripotent stem cells effectively handle DNA replication pressures with unique mechanisms to effectively maintain the stability of genetic material in rapid division.
the application of stem cells in regenerative medicine has great prospects, and the stability of genetic material is the premise of its safe application. Compared
and differentiated cells, stem cells have a short cell cycle, frequent DNA replication, a short G1 phase in the cell cycle, and a lack of G1 cell cycle checkpoints, which make stem cells face great replication pressure in DNA replication.
replication pressure is the main source of endogenous DNA damage and genomic instability, and effective treatment of replication pressure is an important way for cells to maintain the stability of genetic material.
, it is not clear how stem cells can effectively handle replication pressure.
Zheng Ping's team studied the processing power and molecular mechanism of pluripotent stem cells on DNA replication pressure.
by systematically comparing mouse embryonic stem cells with different types of rapidly divided differentiated cells, it is found that pluripotent stem cells have efficient replication pressure processing power, can effectively restart the blocked replication fork, and found the stem cell-specific protein complex filia-Floped, which regulates the efficient restart of replication forks, and expounds its mechanism of action.
specifically, Filia and Floped form a protein complex, where normalization is combined on a replication fork.
when the replication fork is blocked, the Filia-Floped protein complex accumulates in large quantities on the blocked replication fork, and under the regulation of the protein kinase ATR (the core kinase that regulates the replication pressure reaction), Filia's 151st bit fissine is phosphoryrtation, causing the Filia-Floped complex to form a functional scaffolding.
the scaffolding and then efficiently regulate the replication fork restart through two separate channels.
on the one hand, scaffolding protein recruits E3 ubiquitinized enzyme Trim25 to the blocked replication fork, Trim25 by catalyzing its substrate Blm (the key de-rotation enzyme that promotes replication fork restart) to undergo a phenosome modification, thereby recruiting a large amount of Blm to the blocked replication fork to regulate the replication fork restart;
, the pluripotent stem cells thus efficiently maintain replication fork stabilization and restart by adding a Filia-Floped scaffold to the replication fork, which, in a sponge-like manner, quickly enriches a large number of replication fork maintenance and repair factors onto the blocked replication fork.
research has been supported by the national key research and development program stem cell and conversion research projects.
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