DNA repair pathways and cisplatin resistance: an intimate relationship

Loss of DNA mismatch repair in acquired resistance to cisplatin.

Selection of cells for resistance to cisplatin, a well-recognized mutagen, could result in mutations in genes involved in DNA mismatch repair and thereby to resistance to DNA-alkylating agents. Parental cells of the human ovarian adenocarcinoma cell line 2008 expressed hMLH1 when analyzed with immunoblot. One subline selected for resistance to cisplatin (2008/A) expressed no hMLH1, whereas anot...

DNA Repair and Telomeres — An Intriguing Relationship

Platinum resistance: the role of DNA repair pathways.

Although platinum chemotherapeutic agents such as carboplatin, cisplatin, and oxaliplatin are used to treat a broad range of malignant diseases, their efficacy in most cancers is limited by the development of resistance. There are multiple factors that contribute to platinum resistance but alterations of DNA repair processes have been known for some time to be important in mediating resistance....

Recognition and repair of DNA-cisplatin adducts.

Anticancer activity of cisplatin (cis-diamminedichloroplatinum) is believed to result from its interaction with DNA. The drug reacts with nucleophilic sites in DNA forming monoadducts as well as intra- and interstrand crosslinks. DNA-cisplatin adducts are specifically recognized by several proteins. They can be divided into two classes. One constitutes proteins which recognize DNA damage as an ...

DNA Repair Pathways and Mechanisms

Our cells are constantly exposed to insults from endogenous and exogenous agents that can introduce damage into our DNA and generate genomic instability. Many of these lesions cause structural damage to DNA and can alter or eliminate fundamental cellular processes, such as DNA replication or transcription. DNA lesions commonly include base and sugar modifications, singleand double-strand breaks...