The foundational research conducted the University of Pittsburgh by Bennett Van Houten, Ph.D. and others explored how ultraviolet-damaged DNA-binding protein (UV-DDB) protects against cellular sun damage. UV-DDB is a key protein in human global nucleotide excision repair (NER), a multi-step process which eliminates a wide spectrum of damage causing significant distortions in the DNA structure. This is a particularly important process to repair damage from UV light, which accumulates over time as NER capacity decreases.

Single-molecule real-time imaging revealed that UV-DDB forms transient complexes with enzymes that are essential in base excision repair, facilitating their dissociation from DNA in the process. After this damaged DNA has been removed, DNA polymerase is free to patch the remaining single-stranded portion of DNA. Therefore, researchers suggest that UV-DDB is a critical indicator of DNA damage recognition.

Third-generation sequencing, also known as single molecule sequencing, is different from other methods. It utilizes nanopore based technologies that produce short read lengths by fluorescence detection and sequencing by synthesis. Some of the third generation technologies on the market today include: single molecule real-time (SMRT) sequencing by Pacific Biosciences (PacBio) and nanopore sequencing by Oxford Nanopore Technologies.

The researchers also suggest that this discovery has diagnostic relevance in some rare genetic disorders such as xeroderma pigmentosum (non-functional UV-DDB) where patients are virtually guaranteed to develop skin cancer. Conversely, cancer patients with high levels of UV-DDB often respond better to therapies than those with low UV-DDB levels.

“It’s clear this protein is involved in a very fundamental problem,” Van Houten said. “We could not have evolved out of the slime if we didn’t have good DNA repair.”