The function of eukaryotic genomes relies on genetic and epigenetic information. When cells divide, the accurate replication and retention of genetic and epigenetic information is the key to maintaining cell fate, and abnormal changes in these information often cause diseases. TONSOKU (TSK) is a protein that was first found in plants to be involved in DNA replication damage repair, and its homologous protein TONSOKU-like in humans
(TONSL) also has the same function, and TONSL mutations are closely related to some human diseases such as developmental malformations and cancer. It is generally believed that TSK/TONSL recruits DNA damage repair proteins on newly replicated chromatin to maintain the stability of genetic information. However, chromatin duplication also causes dilution of epigenetic information, and whether TSK/TONSL plays a role in the maintenance of epigenetic information is unknown.
The Jiang Danhua research group of the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences found through research that TSK participates in the maintenance of repressive epigenetic modifications such as H3K9me2, H2A.W,
H3K27me3 and DNA methylation. There is direct protein interaction between TSK and H3K9 methyltransferase. In addition, TSK also has genetic and protein interactions with proteins that maintain H3K27me3. These results suggest that TSK may recruit these proteins on nascent chromatin, thereby promoting the restoration of repressive epigenetic modifications after chromatin replication. Since TSK is only associated with nascent chromatin for a short period of time, this also indicates the importance of the rapid recruitment of chromatin-modifying proteins after DNA replication in the maintenance of epigenetic modifications.
The study found a disease-associated protein involved in stabilizing genetic information and maintaining epigenetic information in plants. It provides new possibilities for the pathogenic mechanism of its mutations in the disease.Related results were published inCell
ReportsJournal (https://doi.org/10.1016/j.celrep.2023.112738). Wang Lin, a doctoral student in Jiang Danhua’s research group, and Xue Mande, a graduated doctoral student, are the co-first authors, and researcher Jiang Danhua is the corresponding author. The research was supported by the National Natural Science Foundation of China and the National Key Research and Development Program.