PUBLICATION HIGHLIGHT
The elusive mechanism of DNA repair
Have you ever wondered why sunscreen is so important? Ultraviolet light is emitted from the sun and can damage skin by altering the DNA in skin cells. Specifically, UV light can cause the formation of covalent bonds between adjacent thymine nucleotides on the same DNA strand. However, DNA repair, arguably one of the most important processes in the human body, can prevent DNA damage from developing into skin cancer. Despite this process’ vast importance, the mechanism by which the enzymes involved in DNA repair find the aberrant nucleotides has remained elusive.
SBGrid member Brandt Eichman has been working to elucidate this mechanism. Though it has been believed that modified nucleotide bases are flipped by DNA glycosylases in order to form an active site to facilitate the repair, the researchers have developed the first non-base-flipping mechanism for DNA repair by DNA glycosylases. Mullins et al. monitored the interactions between DNA glycosylase AlkD of Bacillus cereus and an alkylpurine substrate using crystallography, and then recreated the structures of the starting materials, intermediates and products along the reaction coordinate.
In doing this reconstruction, the researchers noticed that the enzyme, DNA glycosylase AlkD, interacted directly with the phosphoribose backbone of the DNA strand without flipping any bases, suggesting a new understanding of the DNA repair pathway. Further, Mullins et al. were able to demonstrate that this non-base-flipping mechanism was followed in vitro and in vivo during DNA repair of damage caused by yatakemycin. Overall, this research suggests a new understanding of the DNA repair mechanism, thus highlighting the importance of understanding how DNA glycosylases function.
Read more in Nature.
Kristen Rodrigues is a graduate of the Harvard-MIT Health Sciences & Technology PhD program in Medical Engineering and Medical Physics with a concentration in Biological Engineering.
Originally published at https://www.tumblr.com on November 22, 2015.
