Details

Autor(en) / Beteiligte

• Hwang, Bor-Jang
• Shi, Gouli
• Lu, A.-Lien

Titel

Mammalian MutY homolog (MYH or MUTYH) protects cells from oxidative DNA damage

Ist Teil von

• DNA repair, 2014-01, Vol.13, p.10-21

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •MYH knockdown human cells are more sensitive to H2O2 than the control cells.•hMYH knockdown cells have altered DNA signaling activation in response to oxidative stress.•hMYH knockdown cells contain higher levels of 8-oxoG lesions than the control cells following H2O2 treatment.•Human cells with overexpression of mouse Myh are more resistant to killing by oxidative stress than control cells.•MYH protects cell from oxidative DNA damage and is critical for proper cellular response to DNA damage. 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.