Two Nature papers refute conventional wisdom: a new paradigm for DNA repair

The work, led by researchers at NYU Grossman School of Medicine, revolves around the sophistication of DNA molecules that are vulnerable to damage by reactive byproducts of cellular metabolism, toxins and UV light

Past research has identified an important search mechanism: transcription-coupled repair relies on RNA polymerase, a large protein machine (complex) that moves along DNA strands and reads instructions as they are transcribed Take the DNA code into the RNA molecule, which then directs the construction of the protein

Including the 2015 Nobel Prize-winning research, scientists generally believe that the TCR plays a relatively small role in repair because it relies on a putative TCR factor that contributes little to DNA repair

Global genome repair (GGR) can scan and repair large portions of DNA independent of transcription

Now, two new studies, published online March 30 in the journals Nature and Nature Communications, agree that most, if not all, NER is based on a first-of-its-kind multistage analysis of DNA repair in live E.

"Based on our findings, we need to rethink some of the fundamental theories in the field of DNA repair," said senior study author Evgeny Nudler, Ph.

Discover new ways

According to the authors, past studies could not fully capture the biological facts of oxygen-tolerant enzymes in bacteria because they used experiments that attempted to recreate complex protein interactions outside living cells

The new study, published in the journal Nature, used a pioneering technique called cross-linking mass spectrometry (XLMS) to map the distances between chemically linked proteins, thereby determining for the first time that a large number of NER and polymerase complexes are active in vivo.

Contrary to conventional theory, the study found RNA polymerase as a scaffold for the assembly of the entire NER complex and as a major sensor of DNA damage

The second study, published in Nature Communications, also in living cells, used a high-throughput sequencing technique called CPD-seq to track the appearance of DNA damage after UV exposure, as well as repair rates, with low resolution to letters (nucleotides) in a single DNA code

Another striking finding was that experiments showed that, in the face of DNA damage, bacterial cells inhibited the action of the protein Rho, a global stop signal that tells RNA polymerase to stop reading

"Given our findings, we reasoned that eukaryotes, including human cells, also use RNA polymerases for efficient repair throughout the body, since the bacterial TCR complex described here is similar to humans," said Nudler, a postdoctoral scholar, Nature Research Co-first author Dr.

Journal References :

1. Martinez, B.

   
   

2. Bharati, BK, Gowder, M.