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Gao-De Li

Publications and source records attributed to Gao-De Li.

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Certain amplified genomic-DNA fragments (AGFs) may be involved in cell cycle progression and chloroquine is found to induce the production of cell-cycle-associated AGFs (CAGFs) in Plasmodium falciparum

It is well known that cyclins are a family of proteins that control cell-cycle progression by activating cyclin-dependent kinase. Based on our experimental results, we propose here a novel hypothesis that certain amplified genomic-DNA fragments (AGFs) may also be required for the cell cycle progression of eukaryotic cells and thus can be named as cell-cycle-associated AGFs (CAGFs). Like fluctuation in cyclin levels during cell cycle progression, these CAGFs are amplified and degraded at different points of the cell cycle. The functions of CAGFs are unknown, but we speculate that CAGFs might be involved in regulation of gene expression, genome protection, and formation of certain macromolecular complexes required for the dynamic genome architecture during cell cycle progression. Our experimental results also show that chloroquine induces the production of CAGFs in Plasmodium falciparum, suggesting that targeting cell cycle progression can be the primary mechanism of chloroquine's antimalarial, anticancer, and immunomodulatory actions.

q-bio.SC

Flexible Cancer-Associated Chromatin Configuration (CACC) Might Be the Fundamental Reason Why Cancer Is So Difficult to Cure

We once proposed that cell-type-associated chromatin configurations determine cell types and that cancer cell type is determined by cancer-associated chromatin configuration (CACC). In this paper, we hypothesize that flexible cell-type-associated chromatin configuration is associated with cell potency and has an advantage over inflexible one in regulating genome related activities, such as DNA replication, DNA transcription, DNA repair, and DNA mutagenesis. The reason why cancer is so difficult to treat is because CACC is flexible, which enables cancer cells not only to produce heterogeneous subclones through limited cell differentiation, but also to maximally and efficiently use genome related resources to survive environmental changes. Therefore, to beat cancer, more efforts should be made to restrict the flexibility of CACC or to change CACC so that cancer cells can be turned back to normal or become less malignant.

q-bio.SC

Further Thoughts on Abnormal Chromatin Configuration and Oncogenesis

More than 30 years ago, we published a paper entitled as abnormal chromatin configuration and oncogenesis, which proposed the first hypothesis that links oncogenesis to abnormal three-dimensional (3D) genome structure. Recently, many studies have demonstrated that the 3D genome structure plays a major role in oncogenesis, which strongly supports our hypothesis. In this paper, further thoughts about our hypothesis is presented.

q-bio.SC

DNA to DNA transcription might exist in eukaryotic cells

Till now, in biological sciences, the term, transcription, mainly refers to DNA to RNA transcription. But our recently published experimental findings obtained from Plasmodium falciparum strongly suggest the existence of DNA to DNA transcription in the genome of eukaryotic cells, which could shed some light on the functions of certain noncoding DNA in the human and other eukaryotic genomes.

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Cell-Cycle-Associated Amplified Genomic-DNA Fragments (CAGFs) Might Be Involved in Chloroquine Action and Resistance in Plasmodium falciparum

As a cheap and safe antimalarial agent, chloroquine (CQ) has been used in the battle against malaria for more than half century. However, the mechanism of CQ action and resistance in Plasmodium falciparum remains elusive. Based on further analysis of our published experimental results, we propose that the mechanism of CQ action and resistance might be closely linked with cell-cycle-associated amplified genomic-DNA fragments (CAGFs, singular form = CAGF) as CQ induces CAGF production in P. falciparum, which could affect multiple biological processes of the parasite, and thus might contribute to parasite death and CQ resistance. Recently, we found that CQ induced one of CAGFs, UB1- CAGF, might downregulate a probable P. falciparum cystine transporter (Pfct) gene expression, which could be used to understand the mechanism of CQ action and resistance in P. falciparum.

q-bio.SC

Nucleus may be the key site of chloroquine antimalarial action and resistance development

The first proposed hypothesis about the mechanism of chloroquine (CQ) action on malaria parasites is DNA intercalation hypothesis which indicates that the site of CQ action is within the nucleus. Later on the interest of research was shifted from nucleus to lysosome due to the report of CQ accumulation within lysosome. The current opinions about CQ action and resistance are mainly based on the results of more than 30-year studies on lysosome, which can be used to explain some facts but still remains incomplete and controversial. Based on recently published papers and our related data it is possible that the key CQ target protein may exist in the nucleus. Development of CQ resistance is probably mainly due to the alteration in the CQ target protein or certain mechanism which prevents CQ from reaching its target protein in the nucleus. In conclusion, the key site of CQ action may be in the nucleus though it has not been well explored while CQ action in lysosome which has been well studied may be secondarily important in CQ action and resistance.

q-bio.SC

Genoautotomy (Genome 'Self-Injury') in Eukaryotic Cells: A Cellular Defence Response to Genotoxic Stress

This paper proposes that eukaryotic cells, under severe genotoxic stress, can commit genoautotomy (genome 'self-injury') that involves cutting and releasing single-stranded DNA (ssDNA) fragments from double-stranded DNA and leaving ssDNA gaps in the genome. The ssDNA gaps could be easily and precisely repaired later. The released ssDNA fragments may play some role in the regulation of cell cycle progression. Taken together, genoautotomy causes limited nonlethal DNA damage, but prevents the whole genome from lethal damage, and thus should be deemed as a eukaryotic cellular defence response to genotoxic stress.

q-bio.SC

A Possible Mechanism of DNA to DNA Transcription in Eukaryotic Cells : Endonuclease Dependent Transcript Cutout

We previously proposed the existence of DNA to DNA transcription in eukaryotic cells, but the mechanism by which single-stranded DNA (ssDNA) transcript is produced and released from the genome remains unknown. We once speculated that the mechanism of DNA to DNA transcription might be similar to that of DNA to RNA transcription, but now we propose that endonuclease dependent transcript cutout may be a possible mechanism of DNA to DNA transcription, in which a copy of ssDNA fragment (transcript) between two nicks produced by nicking endonuclease is released from double-stranded DNA (dsDNA) region in the genome by an unknown ssDNA fragment releasing enzyme. The gap in the dsDNA will be filled through DNA repair mechanism. Occasionally, multiple copies of ssDNA transcripts could be produced through multiple rounds of cutout-repair-cutout cycle.

q-bio.SC

Natural site-directed mutagenesis might exist in eukaryotic cells

Site-directed mutagenesis refers to a man-made molecular biology method that is used to make genetic alterations in the DNA sequence of a gene of interest. But based on our recently published experimental findings, we propose that natural site-directed mutagenesis might exist in the eukaryotic cells, which is triggered by harmful agents and co-directed by special transcription hotspots and mutation-contained intranuclear primers.

q-bio.SC