Japanese scientists elucidate the three-dimensional structure of MUTYH protein and gain an in-depth understanding of DNA repair mechanisms

Japanese researchers have recently analyzed the three-dimensional structure of MUTYH protein at the atomic level and clarified the mechanism of MUTYH's repair of DNA mismatches
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This result was published in the "Nucleic Acids Research" magazine

Since mutations in the MUTYH gene can cause hereditary colorectal polyposis, which leads to colorectal cancer, researchers expect this work to promote future research on hereditary colorectal polyposis associated with MUTYH
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The reactive oxygen species produced in the cell will oxidize DNA, and when the guanine bases in DNA are oxidized, 8-oxoguanine bases will be produced
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Under normal circumstances, guanine pairs with cytosine, but 8-oxoguanine can also pair with adenine, resulting in mutations that may cause cancer and other aging-related diseases

MUTYH is a protein that can detect and remove adenine that is mismatched with 8-oxoguanine
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Previous studies have found that its genetic mutations can lead to hereditary colon polyposis, leading to colorectal cancer

If you want to accurately understand the function of a protein, you must know its structure at the atomic level
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X-ray crystallography is a commonly used method that uses X-rays to study the arrangement of atoms in crystals

Based on the three-dimensional structure of PCNA and MUTYH, the researchers proposed PCNA as a forceps for the DNA double helix, recruiting MUTYH to mismatch sites, which also clarified the mechanism of MUTYH and PCNA to repair DNA together
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In addition, the analysis of the three-dimensional structure of MUTYH and DNA shows that mutations in the MUTYH gene reduce the binding affinity of MUTYH and DNA, making the three-dimensional structure of MUTYH unstable, resulting in a decrease in its DNA repair activity

Associate Professor Teruya Nakamura, the leader of this research, said: “MUTYH and PCNA are known to cooperate with various proteins to participate in DNA repair.

The three-dimensional structure we clarified in this study also lays the foundation for further understanding of DNA repair mechanisms

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Teruya Nakamura, Kohtaro Okabe, Shogo Hirayama, Mami Chirifu, Shinji Ikemizu, Hiroshi Morioka, Yusaku Nakabeppu, Yuriko Yamagata.

Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer.
Nucleic Acids Research, 2021; 49 (12): 7154 DOI: 10.
1093/nar/gkab492