Tel Ad办公空间坐落于以色列卡法萨巴一栋翻新建筑内。因自然采光条件有限,设计团队引入中央人工照明中庭,重塑空间流线,并通过材料运用,明确空间界定与功能分区。该中庭既是空间锚点,亦是氛围焦点。鉴于建筑进深较大,难以持续获取自然...Tel Ad办公空间坐落于以色列卡法萨巴一栋翻新建筑内。因自然采光条件有限,设计团队引入中央人工照明中庭,重塑空间流线,并通过材料运用,明确空间界定与功能分区。该中庭既是空间锚点,亦是氛围焦点。鉴于建筑进深较大,难以持续获取自然光线,中庭采用全光谱农业照明系统,以确保绿植全年茂盛生长。同时,空间流线也经重新设计,形成环绕绿色核心的环形路径,既确保了与绿植的持续视觉联系,又使各工作区域间的流线直观且流畅。除满足空间功能需求外,中庭在提升员工福祉与工作效率方面亦扮演关键角色:研究显示,相较于传统无窗办公环境,接触绿植及动态照明等自然元素,可有效降低压力、增强专注力并缓解视疲劳。室内统一采用水磨石地面、不锈钢装饰及天然木饰面,实现了整体空间的连贯性。展开更多
It has been well documented that Tel1 positively regulates telomere-end resection by promoting Mre11-Rad50-Xrs2（MRX） activity, while Rif2 negatively regulates telomere-end resection by inhibiting MRX activity. At un...It has been well documented that Tel1 positively regulates telomere-end resection by promoting Mre11-Rad50-Xrs2（MRX） activity, while Rif2 negatively regulates telomere-end resection by inhibiting MRX activity. At uncapped telomeres, whether Tel1 or Rif2 plays any role remains largely unknown. In this work, we examined the roles of Tel1 and Rif2 at uncapped telomeres in yku70△ and/or cdc13-1 mutant cells cultured at non-permissive temperature. We found that deletion of TEL1 exacerbates the temperature sensitivity of both yku70△ and cdc13-1 cells. Further epistasis analysis indicated that MRX and Tel1 function in the same pathway in telomere protection. Consistently, TEL1 deletion increases accumulation of Exo1-dependent telomeric single-stranded DNA（ssDNA） at uncapped telomeres, which stimulates checkpoint-dependent cell cycle arrest. Moreover, TEL1 deletion in yku70△ cells facilitates Rad51-dependent Y0 recombination. In contrast, RIF2 deletion in yku70△ cells decreases the accumulation of telomeric ssDNA after 8 h of incubation at the non-permissive temperature of 37℃ and suppresses the temperature sensitivity of yku70△ cells, likely due to the increase of Mre11 association at telomeres.Collectively, our findings indicate that Tel1 and Rif2 regulate telomere protection at uncapped telomeres via their roles in balancing MRX activity in telomere resection.展开更多
基金the support of SA-SIBS scholarship programsupported by the grants from the Ministry of Science and Technology (2016YFA0500701)+2 种基金the National Natural Science Foundation of China (Nos.31230040, 31461143003 and 31521061) to J.-Q.Z.the China Postdoctoral Science Foundation (2015M571611 and 2016T90386)the National Natural Science Foundation of China (No.31500658) to Z.W.
文摘It has been well documented that Tel1 positively regulates telomere-end resection by promoting Mre11-Rad50-Xrs2（MRX） activity, while Rif2 negatively regulates telomere-end resection by inhibiting MRX activity. At uncapped telomeres, whether Tel1 or Rif2 plays any role remains largely unknown. In this work, we examined the roles of Tel1 and Rif2 at uncapped telomeres in yku70△ and/or cdc13-1 mutant cells cultured at non-permissive temperature. We found that deletion of TEL1 exacerbates the temperature sensitivity of both yku70△ and cdc13-1 cells. Further epistasis analysis indicated that MRX and Tel1 function in the same pathway in telomere protection. Consistently, TEL1 deletion increases accumulation of Exo1-dependent telomeric single-stranded DNA（ssDNA） at uncapped telomeres, which stimulates checkpoint-dependent cell cycle arrest. Moreover, TEL1 deletion in yku70△ cells facilitates Rad51-dependent Y0 recombination. In contrast, RIF2 deletion in yku70△ cells decreases the accumulation of telomeric ssDNA after 8 h of incubation at the non-permissive temperature of 37℃ and suppresses the temperature sensitivity of yku70△ cells, likely due to the increase of Mre11 association at telomeres.Collectively, our findings indicate that Tel1 and Rif2 regulate telomere protection at uncapped telomeres via their roles in balancing MRX activity in telomere resection.
