题 目：The Role of N6-Methyladenosine and alkylation repair machinery in Bacterial R-Loop Homeostasis

主 讲：Alexey Ruzov教授

时 间：2026年3月27日（周五）10:00-11:30

地 点：琳恩图书馆111报告厅

报告摘要：

R-loops are ubiquitous regulators of genome stability across all domains of life. While recent studies have implicated N6-methyladenosine (m6A) in mammalian R-loop regulation, its role in prokaryotic R-loop dynamics remains unexplored. Here, we demonstrate that m6A modification of R-loops is an ancient, conserved feature present in Escherichia coli, where it inversely correlates with R-loop abundance. Quantum calculations indicate that m6A-induced helix destabilization is insufficient for autonomous R-loop resolution. Instead, we propose that bacterial R-loop clearance involves m6A-dependent recruitment of RNase H. Furthermore, we identify the oxidative dealkylation enzyme AlkB as a critical regulator of R-loop homeostasis. AlkB depletion dramatically reduces R-loop levels, yet a catalytically inactive mutant substantially rescues this phenotype, suggesting that AlkB stabilizes R-loops via non-catalytic binding to single-stranded DNA. Our findings reveal a fundamental link between alkylation repair machinery and R-loop dynamics and suggest that m6A-dependent genome preservation is an ancestral mechanism conserved between bacteria and eukaryotes.

嘉宾简介：

Alexey Ruzov have long-standing interests in the epigenetic mechanisms of animal development and differentiation. Initially, his research was focused on the biological roles of cytosine DNA methylation (5-methylcytosine, 5mC). He was using amphibian, mouse and cell line models to study biological functions of 5mC-binding proteins. In 2011, he initiated an independent programme in the function and distribution of oxidised forms of 5mC in mammalian stem cells and development. During this time, his work contributed to evaluation of the roles of active demethylation in lineage specification and tumorigenesis. One of his projects aimed at examining the abundance of N6-methyldeoxyadenosine (6mA), in mammalian DNA, rather unexpectedly, led his group to discovery of the presence of its RNA counterpart, N6-methyladenosine (m6A), on RNA:DNA hybrids composing R-loops. These results highlighted m6A as an integral component of these structures pivotal for regulation of their stability and contributing to various aspects of their biology. He is currently focused on deciphering the roles of m6A and other RNA modifications in chromatin regulation and R-loops metabolism.