A new study by Yu Xin of the Institute of Systems Biomedical Research at Peking University found that the anti-cancer gene PTEN is involved in regulating the DNA replication process, as if the discovery of a new "separation" of Sun Wukong, a genomic guardian who protects cells from cancer.
research paper was published as a cover article in Cell Research. Wang Guangxi, a ph.d.m. doctoral student in 2008 basic medicine at Peking University,
, and Li Yang, a 2015 doctoral student, are the co-first authors of the thesis.
experts, PTEN is an important anti-cancer gene, participate in the regulation of a number of cell activities, is to protect cells from cancerous multi-functional defenders, scientists called "Sun Wukong."
DNA replication is recognized as the most basic and important life process in the cell, and the replication fork (the Y-shaped structure formed by the process of de-acting, de-chaining and SSB protein binding on the DNA chain when DNA replication) is like a scaffold in a building, and its stability is very important for the smooth progress of replication.
's new research team found that PTEN plays a key role in the protection of DNA replication forks, and the absence of PTEN can cause the replication fork to collapse, which in turn leads to chromosome instability, and chromosomal instability is very likely to lead to tumor production.
using high-end technologies such as ultra-high resolution imaging, the team observed that PTEN is accurately positioned at the DNA replication point and directly combined with the replication protein RPA1 to promote its aggregation on the replication fork, thus playing the role of protecting the replication fork.
replication protein RPA1 belongs to a specific type of protein within a cell that binds to single-stranded DNA, like a steel pipe and plank on a scaffold.
Yu Xin team found that PTEN can recruit the ubiquitinoprotein OTUB1 de-ubiquitin modification RPA1, maintain its protein stability, maintain adequate RPA1 within the cell, promote its function, protect the replication fork.
the team also established for the first time an RPA1 knockout mouse model, which showed that mice with a hybrid loss of RPA1 were more likely to induce colorectal cancer.
researchers believe that the absence of RPA1 causes the replication fork to collapse, which in turn causes the genome to be unstable, most likely as one of the mechanisms for the production of colorectal cancer, and that the expression of PTEN and RPA1 is likely to be used as a molecular indicator for future diagnosis of colorectal cancer.
PTEN provides a new theoretical basis for the diagnosis and treatment of clinical colon cancer through the model of a stable replication fork in downstream RPA1.
Source: Decoding Medicine.