The vast majority of DNA-damage caused by bioactive molecules such as drugs, toxins, and mutagens falls into just two general categories: alkylation of a DNA nucleophile by an electrophile or the reaction of a pi bond or C-H bond in DNA with a radical intermediate . In the following sections, we will consider the reactions of electrophiles and ...

DNA alkylation includes all modifications induced by the binding of a new alkyl group on a noncanonical position of DNA after monomolecular or bimolecular nucleophilic substitution (SN1/SN2) reactions. 18–20 Alkylation can occur on the oxygen atoms in phosphodiester backbone, as well as on oxygen and nitrogen atoms of the 4 nucleobases. 18,21 ...

DNA Alkylation refers to the process of chemically modifying DNA molecules by attaching alkyl groups to them. This modification can lead to the formation of both monofunctional adducts and bifunctional crosslinks, which can cause damage to the DNA.

2004年11月2日 · Alkylation lesions in DNA and RNA result from endogenous compounds, environmental agents and alkylating drugs. Simple methylating agents, e.g. methylnitrosourea, tobacco-specific nitrosamines and drugs like temozolomide or streptozotocin, form adducts at N- and O-atoms in DNA bases.

DNA alkylation lesions are one of the most common types of DNA damage and can be induced by endogenous compounds, environmental agents, and alkylating drugs used in anticancer therapy. These alkylating agents are mutagenic, toxic, clastogenic, and teratogenic and represent well-known human carcinogens [ 1 ].

DNA alkyltransferase and alkyltransferase-like family proteins are responsible for the repair of highly mutagenic and cytotoxic O 6 -alkylguanine and O 4 -alkylthymine bases in DNA. Their mechanism involves binding to the damaged DNA and flipping the base out of the DNA helix into the active site pocket in the protein.

DNA alkylation refers to the addition of alkyl groups to specific bases, resulting in alkylation products such as O 2 ‐alkylthymine, O 4 ‐alkylthymine, O 6 ‐methylguanine and O 6 ‐ethylguanine, which cause DNA mutations. 11 Human colorectal DNA contains O 6 ‐methylguanine (O6‐MeG) and N 7 ‐methylguanine (N7‐MeG), reflecting ...

2023年2月28日 · DNA alkylation lesions are one of the most common types of DNA damage and can be induced by endogenous compounds, environmental agents, and alkylating drugs used in anticancer therapy. These alkylating agents are mutagenic, toxic, clastogenic, and teratogenic and represent well-known human carcinogens [ 1 ].

2021年9月15日 · Base excision repair (BER) is a conserved, front line DNA repair pathway that removes alkylation damage from DNA. The capacity of BER to repair DNA alkylation varies...

2017年8月7日 · In this study, we systematically investigated the mechanisms contributing to the regiospecific effects of DNA alkylation on pol II-mediated transcription, elucidating important relationships between DNA lesion structure and transcriptional stalling, lesion bypass, and fidelity.