Mismatch repair proteins play a role in ATR activation upon temozolomide treatment in MGMT-methylated glioblastoma.

ABSTRACT: The methylation status of the O⁶-methylguanine methyltransferase (MGMT) gene promoter has been widely accepted as a prognostic biomarker for treatment with the alkylator, temozolomide (TMZ). In the absence of promoter methylation, the MGMT enzyme removes O⁶-methylguanine (O⁶-meG) lesions. In the setting of MGMT-promoter methylation (MGMT-), the O⁶-meG lesion activates the mismatch repair (MMR) pathway which functions to remove the damage. Our group reported that loss of MGMT expression via MGMT promoter silencing modulates activation of ataxia telangiectasia and RAD3 related protein (ATR) in response to TMZ treatment, which is associated with synergistic tumor-cell killing. Whether or not MMR proteins are involved in ATR activation in MGMT-cells

SUBMITTER: Ganesa S 

PROVIDER: S-EPMC8987098 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature