The effect of acidic environment on the repair proces s of O۶ m ethyl guanine b y cysteine

DNA damage that gives rise to aging an d mutation is an impor tant subject from the cancer therapy point of view [۱]. DN A alkylation can be caused by bot h endogeno us and exogenous DNA-damaging agents [۲]. O ۶-methylguanine (O۶mG) readily mispairs with thymine d uring DNA replication that causes GC A T transversion mutatio n. It is known that the O۶-methylguanine-D NA methyltr ansferase ( MGMT) protein which is widely pre sent in alm ost all organi sms, efficiently repairs the O۶mG lesions of D NA to guanine by transferring the m ethyl group from the O۶ site of guanine to th e cysteine r esidue (Cys ۱۴۵ in hum an MGMT) in an irreversible stoic hiometric re action [۳]. This study is focused on the ro le of the acidic enviro nment on th e methyl tra nsfer from O۶mG to Cy s۱۴۵ on the repair process.

Keywords:

O۶- methylguanine-DNA methyltransferase (MGM T) , DNA damage , Cancer therapy , Methylating agent.