RESUMO
Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.
Assuntos
Dano ao DNA/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Transcrição Gênica/genética , Reparo do DNA/genética , Replicação do DNA/genética , Humanos , Mutagênese/genética , Mutagênese/fisiologia , Mutagênicos/toxicidade , Mutação/genéticaRESUMO
A precision laser tracker has been constructed and tested that is capable of tracking a low-acceleration target to an accuracy of about 25 microrad root mean square. In tracking high-acceleration targets, the error is directly proportional to the angular acceleration. For an angular acceleration of 0.6 rad/sec(2), the measured tracking error was about 0.1 mrad. The basic components in this tracker, similar in configuration to a heliostat, are a laser and an image dissector, which are mounted on a stationary frame, and a servocontrolled tracking mirror. The daytime sensitivity of this system is approximately 3 x 10(-10) W/m(2); the ultimate nighttime sensitivity is approximately 3 x 10(-14) W/m(2). Experimental tests were performed to evaluate both dynamic characteristics of this system and the system sensitivity. Dynamic performance of the system was obtained, using a small rocket covered with retroreflective material launched at an acceleration of about 13 g at a point 204 m from the tracker. The daytime sensitivity of the system was checked, using an efficient retroreflector mounted on a light aircraft. This aircraft was tracked out to a maximum range of 15 km, which checked the daytime sensitivity of the system measured by other means. The system also has been used to track passively stars and the Echo I satellite. Also, the system tracked passively a +7.5 magnitude star, and the signal-to-noise ratio in this experiment indicates that it should be possible to track a + 12.5 magnitude star.