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111.
The DNA damage response and cancer therapy 总被引:1,自引:0,他引:1
Genomic instability is one of the most pervasive characteristics of tumour cells and is probably the combined effect of DNA damage, tumour-specific DNA repair defects, and a failure to stop or stall the cell cycle before the damaged DNA is passed on to daughter cells. Although these processes drive genomic instability and ultimately the disease process, they also provide therapeutic opportunities. A better understanding of the cellular response to DNA damage will not only inform our knowledge of cancer development but also help to refine the classification as well as the treatment of the disease. 相似文献
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Farmer H McCabe N Lord CJ Tutt AN Johnson DA Richardson TB Santarosa M Dillon KJ Hickson I Knights C Martin NM Jackson SP Smith GC Ashworth A 《Nature》2005,434(7035):917-921
BRCA1 and BRCA2 are important for DNA double-strand break repair by homologous recombination, and mutations in these genes predispose to breast and other cancers. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in base excision repair, a key pathway in the repair of DNA single-strand breaks. We show here that BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis. This seems to be because the inhibition of PARP leads to the persistence of DNA lesions normally repaired by homologous recombination. These results illustrate how different pathways cooperate to repair damage, and suggest that the targeted inhibition of particular DNA repair pathways may allow the design of specific and less toxic therapies for cancer. 相似文献
114.
The small subunit rRNA (SSrRNA) gene was sequenced for two marine scuticociliates Metanophrys similis and Pseudocohnilembus hargisi. The results show that this gene comprises 1763 and 1753 nucleotides in the two marine ciliates respectively. Metanophrys similis is phylogenetically closely related to the clade containing Mesanophrys carcini and Anophyroides haemophila, which branches basally to other species within the order Philasterida. Pseudocohnilembus hargisi groups with its congener, P. marinus, with strong bootstrap support. Paranophrys magna groups with the clade including Cohnilembus and Uronema, representing a sister clade to that containing the two Pseudocohnilembus species. 相似文献
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Krakauer AH 《Nature》2005,434(7029):69-72
In the few species of birds in which males form display partnerships to attract females, one male secures most or all of the copulations. This leads to the question of why subordinate males help in the absence of observable reproductive benefits. Hamilton's concept of kin selection, whereby individuals can benefit indirectly by helping a relative, was a crucial breakthrough for understanding apparently altruistic systems. However in the only direct test of kin selection in coordinated display partnerships, partners were unrelated, discounting kin selection as an explanation for the evolution of cooperation. Here I show, using genetic measures of relatedness and reproductive success, that kin selection can explain the evolution of cooperative courtship in wild turkeys. Subordinate (helper) males do not themselves reproduce, but their indirect fitness as calculated by Hamilton's rule more than offsets the cost of helping. This result confirms a textbook example of kin selection that until now has been controversial and also extends recent findings of male relatedness on avian leks by quantifying the kin-selected benefits gained by non-reproducing males. 相似文献
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Voyager 2 crossed the solar wind termination shock at 83.7 au in the southern hemisphere, approximately 10 au closer to the Sun than found by Voyager 1 in the north. This asymmetry could indicate an asymmetric pressure from an interstellar magnetic field, from transient-induced shock motion, or from the solar wind dynamic pressure. Here we report that the intensity of 4-5 MeV protons accelerated by the shock near Voyager 2 was three times that observed concurrently by Voyager 1, indicating differences in the shock at the two locations. (Companion papers report on the plasma, magnetic field, plasma-wave and lower energy particle observations at the shock.) Voyager 2 did not find the source of anomalous cosmic rays at the shock, suggesting that the source is elsewhere on the shock or in the heliosheath. The small intensity gradient of Galactic cosmic ray helium indicates that either the gradient is further out in the heliosheath or the local interstellar Galactic cosmic ray intensity is lower than expected. 相似文献
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