Abstract:The DNA damage repair protein O6-methylguanine methyl transferase (MGMT) reverses O6-alkylguanine lesions via SN2 transfer of the alkyl lesion to an active site cysteine which restores DNA to its native state. MGMT is ubiquitously expressed in healthy tissue but is silenced by promoter hypermethylation in approximately half of glioblastomas and up to 75% of lower grade gliomas. As such, patients with MGMT deficient (MGMT-) tumors benefit from DNA alkylation agents such as temozolomide (TMZ), an imidazotetrazin… Show more
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