Dopamine is secreted by the ___________ and is deficient in…

Questions

Dоpаmine is secreted by the _____ аnd is deficient in diseаse.

Dоpаmine is secreted by the _____ аnd is deficient in diseаse.

Dоpаmine is secreted by the _____ аnd is deficient in diseаse.

"The аnti-cаncer efficаcy оf cytоtоxic chemotherapy and radiation is derived from their ability to damage DNA. Analysis of the molecular mechanism of how these treatments damage DNA, and are subsequently repaired, has increased our understanding of the DDR pathway and has exposed potential weakness that can be exploited with molecularly targeted therapies. For example, DNA damage caused by the alkylating chemotherapy temozolomide (TMZ), which is commonly used in glioblastoma and pancreatic neuroendocrine tumors, is repaired by MGMT (methylguanine methyltransferase). This finding provides a rationale for generating pharmacological inhibitors of MGMT that may further sensitize tumors to TMZ. To date, the clinical utilization of MGMT inhibitors, such as O6-benzylguanine, has been hampered by significant myelosuppression (Quinn et al., 2009). Cisplatin mainly exerts damage on DNA by forming intrastrand crosslinks, with the formation of guanine-platinum-guanine and guanine-platinum-adenine adducts (Rocha et al., 2018). While approximately 90% of the crosslinks formed by cisplatin are intrastrand, rarely cisplatin can also generate guanine-platinum-guanine interstrand crosslinks (Rocha et al., 2018). Intrastrand DNA crosslinks are repaired by nucleotide excision repair (NER), a mechanism of single-strand DNA repair which is deficient in patients with xeroderma pigmentosum (Scharer, 2013). Consistent with this, deleterious mutations in an NER pathway helicase, ERRC2, are predictive of cisplatin sensitivity in bladder cancer patients (Van Allen et al., 2014). Repair of interstrand crosslinks, which can also be generated by mitomycin-C, requires both NER and homologous recombination (HR) (Damia and Broggini, 2019; Rocha et al., 2018). Radiation is a particularly effective anti-cancer therapy because it can sever covalent bonds in the DNA phosphodiester backbone and generate double-strand DNA breaks (Toulany, 2019). Bleomycin, a chemotherapy used in the treatment of testicular cancer and Hodgkin’s lymphoma, forms a complex with Fe2+ and O2 and can thereby cleave DNA and generate double-strand DNA breaks (Chen et al., 2008). Topoisomerase I and II enzymes reduce DNA supercoiling by transiently causing single or double-strand DNA breaks, respectively, to allow DNA unwinding. Topoisomerase I inhibitors, such as irinotecan and topotecan, stabilize the topoisomerase I-DNA cleavage complex and prevents the closure of the single-strand DNA break (Pommier et al., 2010). Likewise topoisomerase II inhibitors, like etoposide and doxorubicin, trap the topoisomerase II-DNA cleavage complex and thereby generate a double-strand DNA break (Pommier et al., 2010)." Which DNA repair mechanism is primarily involved in repairing intrastrand crosslinks formed by cisplatin?