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DNA-protein crosslinking can be caused by a variety of chemical and physical agents, including transition metals, ionizing radiation, and endogenous aldehydes, in addition to chemotherapeutic agents. [26] Similar to DNA crosslinking, DNA-protein crosslinks are lesions in cells that are frequently damaged by UV radiation.
DNA crosslinks are caused by numerous anti-cancer drugs (such as cisplatin), but they also must arise naturally since individuals carrying a genetic defect in crosslink repair suffer from the illness Fanconi anaemia. This devastating inherited illness leads to congenital defects, progressive loss of blood production and an enormous lifetime ...
Interstrand crosslinks block the progression of DNA replication, and structures at blocked DNA replication forks provide substrates for cleavage by ERCC1-XPF. [23] [24] Incisions may be made on either side of the crosslink on one DNA strand to unhook the crosslink and initiate repair. Alternatively, a double-strand break may be made in the DNA ...
That marked the start of the Schärer lab - researching chemical, biochemical and cell biological approaches to research nucleotide excision repair, interstrand crosslink repair and how DNA repair pathways impact cancer chemotherapy. [7] The last four years of his time in Zürich, he taught biological chemistry as a lecturer at ETH Zürich.
Some alkylating agents are active under conditions present in cells; and the same mechanism that makes them toxic allows them to be used as anti-cancer drugs. They stop tumor growth by crosslinking guanine nucleobases in DNA double-helix strands, directly attacking DNA. This makes the strands unable to uncoil and separate.
In heterozygous patients, the risk of cancer is sporadic but can be predicted based on analytical assessment of polymorphisms in XP related DNA repair genes purified from lymphocytes. [15] In a study relapse rates of high-risk stage II and III colorectal cancers, XPD (ERCC2) polymorphism 2251A>C was significantly correlated with early relapse ...
A metabolite of benzopyrene forms an intercalated DNA adduct, at center. In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. This process could lead to the development of cancerous cells, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers of exposure.
The main mechanism of cancer development involves increased exposure to acetaldehyde, a carcinogen and breakdown product of ethanol. [41] Acetaldehyde induces DNA interstrand crosslinks, a form of DNA damage. These can be repaired by an inaccurate replication-coupled DNA repair pathway. [42]
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