The p110 Cut homeobox 1 (CUX1) transcription factor regulates genes involved in DNA replication and chromosome segregation. Using a genome-wide-approach, we now demonstrate that CUX1 also modulates the constitutive expression of DNA damage response genes, including ones encoding ATM and ATR, as well as proteins involved in DNA damage-induced activation of, and signaling through, these kinases. Consistently, RNAi knockdown or genetic inactivation of CUX1 reduced ATM/ATR expression and negatively impacted hallmark protective responses mediated by ATM and ATR following exposure to ionizing radiation (IR) and UV, respectively. Specifically, abrogation of CUX1 strongly reduced ATM autophosphorylation after IR, in turn causing substantial decreases in (i) levels of phospho-Chk2 and p53, (ii) γ-H2AX and Rad51 DNA damage foci and (iii) the efficiency of DNA strand break repair. Similarly remarkable reductions in ATR-dependent responses, including phosphorylation of Chk1 and H2AX, were observed post-UV. Finally, multiple cell cycle checkpoints and clonogenic survival were compromised in CUX1 knockdown cells. Our results indicate that CUX1 regulates a transcriptional program that is necessary to mount an efficient response to mutagenic insult. Thus, CUX1 ensures not only the proper duplication and segregation of the genetic material, but also the preservation of its integrity.
The purpose of this research is to investigate long term effects of cognitive skill degradation through the use of automation. Even though advanced studies have looked into information automation (IA) in aviation, the amount of empirical data on the effects of these systems on the retention of cognitive skills is less deeply examined. Measurement and analysis of the effects of IA on cognitive performance is an important first step in understanding cognitive skill degradation, which should be considered during the design of these systems. The use of an automation aid is expected to result in a high level of performance degradation over time. Participants were randomly placed into three experimental groups (manual, alternating, or automation) and asked to perform flight planning calculations as an experiment task. Participants performed the task five times, once every two weeks. The manual group used the manual method throughout the experiment, the alternating group switched between the manual and automated method every trial. The automation group used the manual method for the first trial, the automated method for the three consecutive trials and then went back to using the manual method during the last trial. The automation group showed the most performance degradation and highest workload, while the alternating group presented reduced performance degradation and workload, and the manual group showed the least performance degradation and workload. This work provides the foundation for the design of guidelines and recommendations for IA systems in order to prevent cognitive skill degradation.
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