title: Mammalian MutY homolog (MYH or MUTYH) protects cells from oxidative DNA damage.
abstract: MutY DNA glycosylase homologs (MYH or MUTYH) reduce G:C to T:A mutations by removing misincorporated adenines or 2-hydroxyadenines paired with guanine or 8-oxo-7,8-dihydroguanine (8-oxo-G). Mutations in the human MYH (hMYH) gene are associated with the colorectal cancer predisposition syndrome MYH-associated polyposis. To examine the function of MYH in human cells, we regulated MYH gene expression by knockdown or overproduction. MYH knockdown human HeLa cells are more sensitive to the killing effects of H2O2 than the control cells. In addition, hMYH knockdown cells have altered cell morphology, display enhanced susceptibility to apoptosis, and have altered DNA signaling activation in response to oxidative stress. The cell cycle progression of hMYH knockdown cells is also different from that of the control cells following oxidative stress. Moreover, hMYH knockdown cells contain higher levels of 8-oxo-G lesions than the control cells following H2O2 treatment. Although MYH does not directly remove 8-oxo-G, MYH may generate favorable substrates for other repair enzymes. Overexpression of mouse Myh (mMyh) in human mismatch repair defective HCT15 cells makes the cells more resistant to killing and refractory to apoptosis by oxidative stress than the cells transfected with vector. In conclusion, MYH is a vital DNA repair enzyme that protects cells from oxidative DNA damage and is critical for a proper cellular response to DNA damage.
authors: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, United States.
authors: Bor-Jang
authors: BJ
authors: Hwang
authors: University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, United States.
authors: Gouli
authors: G
authors: Shi
authors: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, United States; University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, United States. Electronic address: aluchang@umaryland.edu.
authors: A-Lien
authors: AL
authors: Lu
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D045647:DNA Glycosylases / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018384:Oxidative Stress; D015398:Signal Transduction / Q000235:genetics
chemical_list: D006151:Guanosine; C046215:8-hydroxyguanosine; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
keywords: Base excision repair; DNA damage response; DNA repair; MutY homolog; Oxidative stress