Researchers reveal how PICH protein protects DNA during cell division

Researchers at the University of Hong Kong (HKU) have made exciting discoveries about how human cells protect their DNA during cell division, providing new insights into the fight against diseases such as cancer. .

The study, led by Professor Gary Ying Wai CHAN from the Faculty of Science's School of Biological Sciences and Professor Ken Hoi Tang MA from the Department of Pathology at the LKS Faculty of Medicine, revealed the important role of a protein called PICH in preventing genetic errors. It can cause diseases such as cancer. Their findings were recently published in the journal Nucleic acid research.

Ultra-fine late bridges – a hidden threat to our genome

Every time a cell divides, its DNA must be copied accurately and split between the two new cells. However, tiny strands of DNA known as ultra-fine late bridges (UFBs) form and can cause problems if not managed properly. These UFBs can be thought of as invisible enemies that entangle our genetic material.

Through research, the HKU team discovered that the protein PICH acts like a radar, detecting these UFBs and helping to resolve them. They say that when PICH is missing or not functioning properly, cells develop serious genetic problems such as DNA damage, the formation of small DNA-containing structures called micronuclei, and activation of the cell's emergency response system. They found that cells experience damage that ultimately leads to cell death. Furthermore, their findings revealed that such damage can cause chromosomal rearrangements that are a hallmark of cancer.

PICH prevents dangerous rearrangements of DNA

Based on these findings, the team further investigated the role of PICH in maintaining genetic stability. They found that without PICH, cells not only suffer severe DNA damage but also accumulate significant genetic errors. Mutated versions of PICH that are unable to recruit other helper proteins provide only partial protection, whereas fully inactive versions of PICH are unable to resolve UFB and result in more extensive genetic damage. PICH activity is important to disrupt these DNA strands and prevent genetic disruption. In particular, when PICH is deficient, UFB damage is likely to cause genetic errors in noncentromeric regions of DNA, leading to dangerous chromosomal rearrangements that can cause disease.

Their study proposes that PICH protects human DNA through two important mechanisms. First, another protein, topoisomerase IIα (TOP2A), helps unwind the DNA. It then works with a protein called BLM helicase to transform the tangled thread into a simpler, more manageable form. These two actions ensure that DNA threads resolve properly and prevent genetic errors that can lead to cancer.

Our study shows how important PICH is in protecting DNA from damage during cell division. Understanding how PICH works can explore new ways to treat cancers such as colorectal, gastric, and breast cancers, which are strongly associated with high degrees of chromosomal instability. ”

Professor Gary Ying Wai Chan, one of the paper's corresponding authors

“Next generation sequencing (NGS) is a powerful tool for detecting genomic instability in diseases such as cancer. In our study, we used NGS to This productive collaboration with Professor Chan emphasized the importance of teamwork in scientific research.” added Professor Keng Hui Tan Ma, the study's other corresponding author.

This study highlights the important role of PICH in maintaining the integrity of human genetic material. Understanding how PICH works opens new possibilities for developing treatments for diseases caused by genetic instability, such as cancer. “Targeting the pathways involved in PICH may allow us to develop new treatments to prevent or treat these conditions,” explained Professor Gary Yin Wai Chan.

The findings are detailed in the paper “Interaction of translocase activity and protein recruitment function of PICH in resolution and genome stability of ultrafine late bridges”published in a magazine Nucleic acid research.