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Scientists elucidate the inner workings of DNA repair enzymes

Mechanism of gap formation by multifunctional nuclease during base excision repair.Credit: Gwangju Institute of Science and Technology

DNA is the instruction manual for all living organisms and guides the development and function of all biological processes. In essence, it is a molecule with a double helix structure, and each unit of the helix contains what is known as a “DNA base.”

Maintaining DNA is very important for the smooth operation of all physical functions. DNA can be damaged by cell metabolism by-products such as reactive oxygen species and ionizing radiation (UV and gamma rays). In such a scenario, a series of enzymes (proteins that act as catalysts for biochemical reactions) are activated and the damage is repaired. The sequence of processes performed by enzymes to repair DNA damage is known as “base excision repair” (BER).

BER is primarily performed by the exonuclease III (ExoIII) and polymerase I (Pol I) enzymes. Despite the importance of the function of these enzymes, the underlying mechanisms of their coordination have not been elucidated in previous studies.

Currently, scientists led by Dr. Gwangrog Lee of the Gwangju Institute of Science and Technology (GIST) in South Korea are using the latest version. technology It bridges the gap in understanding this regulatory mechanism in single molecule detection for studying enzyme interactions and observing the mechanism of BER.

In their treatise published in Science AdvancesScientists have reported that ExoIII has an affinity for the aprine / apyrimidine (AP) site of damaged DNA (a spot on the DNA double helix lacking a DNA sequence). It attaches to the AP site of damaged DNA and digests a number of bases selected from other strands to break the double strand of DNA into a single strand. ExoIII is very sensitive to salt concentration, so the number of bases digested and the resulting gap size depend on the physiological salt state. PolI then attaches to the 3′(3 prime end) of the digested DNA strand and fills the gap.

“Interestingly, there is complete temporal and spatial regulation between Exo III gap-building activity and Pol I gap-filling activity, and genomic stability is always maintained,” said Dr. Lee. Emphasizes the core of.

Understanding the role of Exo III in BER has opened several doors for future research.For example, expression of AP endonuclease cancer cell Much higher than Normal cells, AP endonucleases (eg ExoIII and APE1) can be used as biomarkers for cancer diagnosis. “This study provides insights into the manipulation mechanisms of other enzymes involved in DNA repair. Further research in this area may lead to techniques for target gene repair. Drug development“Dr. Lee concludes.

Pathways that did not move much in DNA double-strand break repair

For more information:
Jungmin Yoo et al, Mechanism of gap formation by multifunctional nucleases during base excision repair, Science Advances (2021). DOI: 10.1126 / sciadv.abg0076

Provided by GIST (Gwangju Institute of Science and Technology)

Quote: Under the Scanner: Scientists Obtained DNA Repair Enzymes (2021) from on September 13, 2021 Elucidate the internal function of (September 13, 2014)

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Source: on 2021-09-13 15:30:00

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