BRCA1 is a well-established tumor suppressor gene,which is frequently mutated in familial breast and ovarian cancers.The gene product of BRCA1 functions in a number of cellular pathways that maintain genomic stability...BRCA1 is a well-established tumor suppressor gene,which is frequently mutated in familial breast and ovarian cancers.The gene product of BRCA1 functions in a number of cellular pathways that maintain genomic stability,including DNA damage-induced cell cycle checkpoint activation,DNA damage repair,protein ubiquitination,chromatin remodeling,as well as transcriptional regulation and apoptosis.In this review,we discuss recent advances regarding our understanding of the role of BRCA1 in tumor suppression and DNA damage response,including DNA damage-induced cell cycle checkpoint activation and DNA damage repair.展开更多
The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusi...The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.展开更多
p53 is a key transcription factor to regulate gene transcription.However,the molecular mechanism of chromatin-associated p53 on gene transcription remains elusive.Here,using unbiased protein affinity purification,we f...p53 is a key transcription factor to regulate gene transcription.However,the molecular mechanism of chromatin-associated p53 on gene transcription remains elusive.Here,using unbiased protein affinity purification,we found that the RNF20/40 complex associated with p53 on the chromatin.Further analyses indicated that p53 mediated the recruitment of the RNF20/40 complex to p53 target gene loci including p21 and PUMA loci and regulated the transcription of p21 and PUMA via the RNF20/40 complex-dependent histone H2B ubiquitination(ubH2B).Lacking the RNF20/40 complex suppressed not only ubH2B but also the generation of the mature mRNA of p21 and PUMA.Moreover,ubH2B was recognized by the ubiquitin-binding motif of pre-mRNA processing splicing factor 8(PRPF8),a subunit in the spliceosome,and PRPF8 was required for the maturation of the mRNA of p21 and PUMA.Our study unveils a novel p53-dependent pathway that regulates mRNA splicing for tumor suppression.展开更多
现代生物学和生物医学领域迫切需要研制兼顾大视场、高分辨率的显微成像技术和仪器以对生物样品实现跨尺度观测,满足重大科学问题的研究需求。受限于系统的空间带宽积,传统商业显微镜无法满足这一需求,且现有高空间带宽积显微成像系统...现代生物学和生物医学领域迫切需要研制兼顾大视场、高分辨率的显微成像技术和仪器以对生物样品实现跨尺度观测,满足重大科学问题的研究需求。受限于系统的空间带宽积,传统商业显微镜无法满足这一需求,且现有高空间带宽积显微成像系统存在体积庞大、实施成本高昂等问题。本文基于HiLo光切片技术和自主设计的大视场高分辨显微物镜,研发了具有高空间带宽积特点的大视场高分辨HiLo光切片显微成像系统,测试了系统的成像视场和分辨率。应用该系统对小鼠脑切片开展了白光照明明场成像实验,并与OLYMPUS商业显微镜成像结果做了对比;对小麦种子荧光切片开展了光切片成像和宽场荧光成像对比实验。实验结果表明,大视场高分辨HiLo光切片显微成像系统的成像视场达到4.8 mm×3.6 mm (对角视场为6.0 mm),横向分辨率达到0.74μm,轴向分辨率达到4.16μm。大视场高分辨HiLo光切片显微成像系统兼有大视场和高分辨率成像的优势和快速光切片成像的能力,能够对大体积生物样本开展快速三维成像,将为胚胎发育、脑成像、数字病理诊断等研究提供有力的技术支撑。展开更多
基金This work was supported in part by grants from the National Institutes of Health(CA132755 to XY)the Developmental fund from the University of Michigan Cancer Center.
文摘BRCA1 is a well-established tumor suppressor gene,which is frequently mutated in familial breast and ovarian cancers.The gene product of BRCA1 functions in a number of cellular pathways that maintain genomic stability,including DNA damage-induced cell cycle checkpoint activation,DNA damage repair,protein ubiquitination,chromatin remodeling,as well as transcriptional regulation and apoptosis.In this review,we discuss recent advances regarding our understanding of the role of BRCA1 in tumor suppression and DNA damage response,including DNA damage-induced cell cycle checkpoint activation and DNA damage repair.
基金financially supported by grants from the National Natural Science Foundation of China,No.81371346,81271376Outstanding Postgraduate Fund of Xinxiang Medical UniversityScience and Technology Key Research Project of Henan Provincial Education Department of China,No.14A310019
文摘The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.
基金This work was supported by the National Natural Science Foundation of China(31670812 to C.W.)the grant for Returned Overseas Chinese Scholars of Hebei Province(CY201602 to C.W.)+1 种基金the Hundreds of Outstanding Talent Innovation Projects in Hebei Province(SLRC2017023 to C.W.)the Natural Science Foundation of Hebei Province(C2018201171 to C.W.).
文摘p53 is a key transcription factor to regulate gene transcription.However,the molecular mechanism of chromatin-associated p53 on gene transcription remains elusive.Here,using unbiased protein affinity purification,we found that the RNF20/40 complex associated with p53 on the chromatin.Further analyses indicated that p53 mediated the recruitment of the RNF20/40 complex to p53 target gene loci including p21 and PUMA loci and regulated the transcription of p21 and PUMA via the RNF20/40 complex-dependent histone H2B ubiquitination(ubH2B).Lacking the RNF20/40 complex suppressed not only ubH2B but also the generation of the mature mRNA of p21 and PUMA.Moreover,ubH2B was recognized by the ubiquitin-binding motif of pre-mRNA processing splicing factor 8(PRPF8),a subunit in the spliceosome,and PRPF8 was required for the maturation of the mRNA of p21 and PUMA.Our study unveils a novel p53-dependent pathway that regulates mRNA splicing for tumor suppression.
文摘现代生物学和生物医学领域迫切需要研制兼顾大视场、高分辨率的显微成像技术和仪器以对生物样品实现跨尺度观测,满足重大科学问题的研究需求。受限于系统的空间带宽积,传统商业显微镜无法满足这一需求,且现有高空间带宽积显微成像系统存在体积庞大、实施成本高昂等问题。本文基于HiLo光切片技术和自主设计的大视场高分辨显微物镜,研发了具有高空间带宽积特点的大视场高分辨HiLo光切片显微成像系统,测试了系统的成像视场和分辨率。应用该系统对小鼠脑切片开展了白光照明明场成像实验,并与OLYMPUS商业显微镜成像结果做了对比;对小麦种子荧光切片开展了光切片成像和宽场荧光成像对比实验。实验结果表明,大视场高分辨HiLo光切片显微成像系统的成像视场达到4.8 mm×3.6 mm (对角视场为6.0 mm),横向分辨率达到0.74μm,轴向分辨率达到4.16μm。大视场高分辨HiLo光切片显微成像系统兼有大视场和高分辨率成像的优势和快速光切片成像的能力,能够对大体积生物样本开展快速三维成像,将为胚胎发育、脑成像、数字病理诊断等研究提供有力的技术支撑。
