An important discovery in cancer research
Bratislava, 23 February 2021: Slovak scientists discovered that the proteins which facilitate homologous recombination - a type of emergency repair of large-scale DNA damage - can be used to regulate the on/off switching of more than 500 genes. Until now scientists have thought that the proteins were only involved in DNA repair. In humans, this mechanism might play a role in oncological diseases. This discovery opens the potential for further cancer research. The study, published in the well-respected Nucleic Acids Research journal at the end of January, was produced by a team of scientists led by Silvia Bágeľová Poláková from the Slovak Academy of Sciences and Tomáš Szemes from Comenius University Bratislava (CU). The journal where the article was published belongs among the most prestigious publications in biochemistry.
Whenever DNA becomes damaged, the body engages mechanisms to repair it. One of the most serious types of DNA damage occurs when double-strand breaks appear. Improper repair of these breaks can result in cancer or cell death. Homologous recombination is one of two major pathways responsible for repairing such double-strand breaks in DNA. Slovak researchers have now discovered an interplay between the homologous recombination pathway and the HIRA complex.
"The HIRA complex plays a significant role in regulating the on/off switching of multiple genes. Its activity also prevents viral DNA from affecting the human genome, thus contributing to internal antiviral immunity," explains Tomáš Szemes from the CU Science Park.
Researchers from the Slovak Academy of Sciences Ivana Mišová and Alexandra Piteľová discovered that the homologous recombination pathway affects the transcription of more than 500 genes. Using comparative analysis they showed that the HIRA complex regulates the same type of genes. Remarkably, the genes regulated by this mechanism are located near the 'LTR retrotransposons’. These are mobile elements in the genome that appear to have a common origin with retroviruses.
An extensive analysis performed by two bioinformaticians from the CU Science Park Jaroslav Budiš and Juraj Gazdarica helped obtain detailed knowledge about the impact of incorrect emergency DNA repair on gene expression.
The authors plan to develop the potential of the discovery in follow-up research. The team of scientists will continue to study the mechanism through which the homologous recombination pathway is also involved in the regulation of DNA transcription, because so far it has only been associated with DNA damage repair.
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RNDr. Tomáš Szemes, PhD., Mgr. Jaroslav Budiš, PhD., Mgr. Juraj Gazdarica, RNDr. Tatiana Sedláčková, PhD., Mgr. Mária Šmondrková, Mgr. Nina Mayerová and Mgr. Lucia Striešková, PhD., work at Comenius University Bratislava.
Mgr. Silvia Bágeľová Poláková, PhD., Mgr. Ivana Mišová, Mgr. Alexandra Piteľová, Mgr. Zsigmond Benko, Mgr. Karoline Pichlerová and Ing. Ľuboš Cipák, PhD., work at the Slovak Academy of Sciences.
Mgr. Anna Jordáková and RNDr. Martin Převorovský, Ph.D., work at Charles University Prague.
Doc. Mgr. Juraj Gregáň, DrSc., works at the University of Vienna.
The research was published by the Nucleic Acids Research journal: https://doi.org/10.1093/nar/gkab027