Researchers Use XR-seq to Identify the Proteins and Mechanisms Behind Bacterial DNA Repair

A team of scientists has just discovered two major proteins associated with bacterial DNA repair. The proteins help bacteria repair any damage that may have occurred to their genome and researchers have now mapped this process. The findings may lead to new antibacterial drugs in the future and a better understanding of human DNA repair. The details were published in the journal Proceedings of the National Academy of Sciences.

It’s hard to imagine, but our DNA is damaged every single day. Luckily, there are molecular repair mechanisms in place to find and fix mutations or other forms of damage. One type of repair method, excision repair, cuts out damaged sections of DNA, allowing the strand to be fixed. This method is generally used to eliminate mutations caused by exposure to ultraviolet light. Although this mechanism is used in both human and bacterial cells, there are still a lot of unanswered questions about the molecular details behind excision repair.

Researchers from the UNC School of Medicine, including Nobel Prize winner Aziz Sancar, studied the molecular mechanisms behind excision repair in Escherichia coli bacteria. The team recently developed a technique called eXcision Repair-sequencing (XR-seq) and used it in their study. XR-seq allows researchers to track exactly which pieces of DNA are snipped during excision repair. When DNA is exposed to ultraviolet light, mutations called thymine dimers can pop up, leading to lesions. XR-seq shows scientists which regions will be repaired first and which will be fixed later. This technique was used to create a DNA repair map of the human genome but can be applied to other organisms.

The research team exposed E.coli bacteria to ultraviolet rays to induce mutations, allowing the team to identify the key mechanisms behind bacterial DNA repair. After exposure, the researchers used XR-seq to track sections of the genome that were being repaired. The team first focused on a protein called Mfd. They found that repairs were only occurring in cells that contained this protein. Further analysis showed that Mfd was responsible for activating proteins that cut out damaged DNA for replacement. Mfd also plays a role in aiding the repair process by reactivating molecular machinery that may have gotten “stuck” due to lesions or other damage. A second protein, UvrD, unwinds the damaged DNA that has been cut out of the strand, making it possible for other proteins to clean up. XR-seq confirmed that both Mfd and UvrD are necessary for quick and efficient DNA excision repair.

The team’s findings provide new insights into how bacteria repair genomic damage. This could lead to the development of better antibacterial drugs while helping scientists learn more about DNA repair in multicellular organisms, including humans.

REFERENCE

Abedali et al. Genome-wide transcription-coupled repair in Escherichia coli is mediated by the Mfd translocase. Proceedings of the National Academy of Sciences (2017).

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