As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identi...As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.展开更多
Deformation resulting from residual stress has been a significant issue in machining.As allowance allocation can directly impact the residual stress on part deformation,it is essential for deformation control.However,...Deformation resulting from residual stress has been a significant issue in machining.As allowance allocation can directly impact the residual stress on part deformation,it is essential for deformation control.However,it is difficult to adjust allowance allocation by traditional simulation methods based on residual stress,as the residual stress cannot be accurately measured or predicted,and many unexpected factors during machining process cannot be simulated accurately.Different from traditional methods,this paper proposes an allowance allocation method based on dynamic approximation via online inspection data for deformation control of structural parts.An Autoregressive Integrated Moving Average(ARIMA)model for dynamic allowance allocation is established so as to approach the minimum deformation,which is based on the in-process deformation inspection data during the alternative machining process of upside and downside.The effectiveness of the method is verified both by simulation cases and real machining experiments of aircraft structural parts,and the results show that part deformation can be significantly reduced.展开更多
文摘As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.
基金co-supported by the National Natural Science Foundation of China(No.51775278)National Science Fund of China for Distinguished Young Scholars(No.51925505)。
文摘Deformation resulting from residual stress has been a significant issue in machining.As allowance allocation can directly impact the residual stress on part deformation,it is essential for deformation control.However,it is difficult to adjust allowance allocation by traditional simulation methods based on residual stress,as the residual stress cannot be accurately measured or predicted,and many unexpected factors during machining process cannot be simulated accurately.Different from traditional methods,this paper proposes an allowance allocation method based on dynamic approximation via online inspection data for deformation control of structural parts.An Autoregressive Integrated Moving Average(ARIMA)model for dynamic allowance allocation is established so as to approach the minimum deformation,which is based on the in-process deformation inspection data during the alternative machining process of upside and downside.The effectiveness of the method is verified both by simulation cases and real machining experiments of aircraft structural parts,and the results show that part deformation can be significantly reduced.
