DNA Repair Mechanisms: Varun Kumar Receives DFG Grant
Dr. Varun Kumar from Helmholtz Munich has been awarded a grant from the German Research Foundation (DFG) to study how cells repair damaged DNA, with a focus on a protein called nuclear RAGE (nRAGE). This funding will support research aimed at uncovering how tiny chemical changes to nRAGE, known as post-translational modifications (PTMs), control its role in fixing DNA damage. The goal is to better understand how problems in this repair process contribute to diseases like diabetic lung fibrosis, aging and cancer. The findings could pave the way for new treatments targeting these diseases.
The Importance of DNA Repair
DNA repair is essential for protecting our genetic information, especially when it gets damaged by environmental or internal factors. When these repair systems are disrupted, it can lead to serious issues like premature aging, organ failure, or disease. Dr. Kumar’s research aims to uncover how a key protein, nRAGE, plays a central role in coordinating DNA repair. Specifically, he is studying how nRAGE helps regulate important repair processes, such as homologous recombination (HR), and how it responds to stress during DNA replication and to certain types of DNA damage, like interstrand crosslinks (ICLs).
New Avenues for Understanding Disease Mechanisms
The protein nRAGE plays a crucial role in coordinating how DNA repair mechanisms work together, but how it is regulated by chemical changes like phosphorylation and acetylation is not yet fully understood. The DFG-funded research project aims to explore this by focusing on two main goals. First, researchers will investigate how phosphorylation – adding a phosphate group to nRAGE – affects DNA repair, including its role in responding to double-strand breaks in DNA, persistent damage signaling, and the onset of cellular aging (senescence). Secondly, the project will examine how acetylation – another type of chemical modification – regulates nRAGE during DNA repair and will identify the key factors that remove acetyl groups from nRAGE under conditions of DNA damage. This research could lead to important insights into how nRAGE helps repair damaged DNA and how failures in these processes may contribute to disease like cancer and aging.
The Role of DNA Damage in Diabetic Complications
In addition to the successfully acquired grant, Kumar and his colleagues Prof. Ali Önder Yildirim and Prof. Peter P. Nawroth recently published a commentary in Nature Reviews Endocrinology. The article sheds light on the connection between DNA damage and the progression of diabetic complications and delves into how chronic high blood sugar levels in diabetes can cause DNA damage, contributing to serious conditions such as diabetic kidney disease, pneumopathy, and cardiovascular disease. The researchers discuss the molecular pathways involved in DNA damage and repair in diabetic patients, highlighting how impaired DNA repair mechanisms might worsen the long-term effects of diabetes. The publication proposes that targeting these pathways could offer new therapeutic opportunities to treat or prevent the complications of diabetes.
Original publication
Kumar, Yildirim and Nawroth (2024): The role of DNA damage in diabetic complications. Nature Reviews Endocrinology. DOI: 10.1038/s41574-024-01038-z
