Researchers have made a groundbreaking discovery about the mechanisms through which human cells safeguard DNA during cell division. This finding could lead to innovative strategies for tackling diseases like cancer. The study highlights the crucial function of a protein named PICH in averting genetic mistakes that may result in conditions such as cancer.
Researchers at The University of Hong Kong (HKU) have made an exciting discovery about how human cells protect DNA during cell division, offering new insights into combating diseases such as cancer.
Headed by Professor Gary Ying Wai CHAN from the School of Biological Sciences and Professor Ken Hoi Tang MA from the Department of Pathology at LKS Faculty of Medicine, the research reveals the essential role of a protein known as PICH in stopping genetic errors that can cause diseases like cancer. Their research findings were published in the journal Nucleic Acids Research.
Ultrafine Anaphase Bridges — A Hidden Threat to Our Genome
When a cell splits, it needs to ensure that its DNA is precisely duplicated and divided between the two daughter cells. However, when tiny strands of DNA, referred to as ultrafine anaphase bridges (UFBs), form, they can lead to complications if not addressed properly. These UFBs can be seen as unseen adversaries that tangle with our genetic information.
The HKU team discovered that the protein PICH functions like a radar, identifying these UFBs and assisting in their resolution. They observed that in the absence of PICH or if it fails to function correctly, cells suffer from significant genetic damage, such as broken DNA and the creation of small DNA-containing bodies known as micronuclei. Additionally, the cell’s emergency response systems become activated, which can ultimately lead to cell death. Further, their research also indicated that such damage could result in chromosome rearrangements, a characteristic of cancer.
PICH prevents dangerous rearrangements of DNA
Building on their findings, the researchers looked deeper into the function of PICH in preserving genetic stability. They discovered that a lack of PICH not only leads to serious DNA harm but also results in the accumulation of considerable genetic mistakes. A mutant version of PICH that cannot attract other helper proteins offers only limited protection, while a completely inactive form of PICH fails to handle UFBs effectively, resulting in even more extensive genetic harm. PICH’s activity is crucial for dismantling these DNA threads and curbing genetic disorder. Importantly, when PICH is absent, there is an increased risk of genetic errors occurring in non-centromeric regions of DNA due to UFB breakage, leading to harmful chromosome rearrangements that can cause disease.
Their study suggests that PICH safeguards human DNA through two main processes. First, it aids another protein, topoisomerase IIα (TOP2A), in untangling DNA strands. Second, it collaborates with the protein BLM helicase to transform tangled strands into a simpler, more manageable shape. These combined actions ensure that DNA strands are effectively resolved, preventing genetic errors that could lead to cancer.
“Our research emphasizes the importance of PICH in protecting our DNA from damage during cell division. By understanding how PICH operates, we can explore new treatment avenues for cancers such as colorectal, gastric, and breast cancer, which are closely associated with high levels of chromosomal instability,” stated Professor Gary Ying Wai Chan, one of the lead authors of the study.
“Next-generation sequencing (NGS) is a robust tool for identifying genomic instability in diseases like cancer. In our study, we utilized NGS to detect mutations in cells lacking PICH, demonstrating its effectiveness in revealing genetic errors. This successful collaboration with Professor Chan has underscored the significance of teamwork in scientific exploration,” added Professor Ken Hoi Tang Ma, another lead author of the research.
This study underscores the vital role of PICH in preserving the integrity of human genetic material. By understanding the workings of PICH, new opportunities for developing treatments for genetic instability-related diseases, including cancer, become apparent. “By targeting pathways associated with PICH, we might develop novel therapies to prevent or treat these conditions,” explained Professor Gary Ying Wai Chan.
