【正文】 which a base sequence changes is called mutation. ? At the nucleotide level, there are two principal mechanisms of mutation: – A chemical alteration of the base that gives it new hydrogenbonding properties and, thus, causes a different base to be incorporated into the daughter DNA strand during subsequent replication. – A replication error by which an incorrect base is erroneously incorporated, or an extra base is accidentally inserted or deleted in the daughter molecule. ? On the average, mutational changes are deleterious and may lead to cell death or impaired function. Molecular Biology 大連理工大學 Summary ? Early experimental evidence that identified DNA as the geic material ? Understand the experimental design and ideas ? RNA as the geic material in some viruses ? Properties of geic material ? Prion: PrPc vs PrPsc ? Transmissible spongiform encephalopathies ? Prion biology ? The key event in the pathogenesis of TSE The end of chapter 6 Molecular Biology 大連理工大學 謝謝觀看 /歡迎下載 BY FAITH I MEAN A VISION OF GOOD ONE CHERISHES AND THE ENTHUSIASM THAT PUSHES ONE TO SEEK ITS FULFILLMENT REGARDLESS OF OBSTACLES. BY FAITH I BY FAITH 。 ? Some researchers speculate that prions are not needed for “routine” functions but somehow enable the nervous system to “finetune” itself at the cellular level ? Other studies: 1. prionlike properties to a mechanism involved in maintaining memory 2. involvement in the immune system 3. function in circadian rhythm and sleep regulation Molecular Biology 大連理工大學 Abnormal Prion: PrPsc ? same amino acid sequence as normal prion . their primary structure is the same but their secondary structure is dominated by beta confirmation ? resists normal degradation techniques . formaldehyde, temperature, UV light, proteases nucleases ? Stimulates no immune response in the host Molecular Biology 大連理工大學 The key event in the pathogenesis Normal Prions contain majorlyαhelix Abnormal Prions have moreβsheet conformational conversion of a normal cell surface glycoprotein (PrP C ) into a pathogenic isoform (PrP Sc ) Molecular Biology 大連理工大學 Prion biology ? For a prion (PrPSc) to infect a host, the host must have a recognizable cellular form (PrPc) of that prion ? Generally, the closer the phylogeic relationship between the donor host and the recipient, the greater the chance for infection, and the more rapidly symptoms occur ? Level of accumulation of prion does not necessarily correspond to level of disease ? Pathologic effect occurs when a normal PrPc protein is converted to PrPsc protein in the endosomal partment of the cell, and is no longer recycled back to the surface of the cell ? when the PrPsc protein begins to accumulate in the endosomal partments, amyloid（ 淀粉樣） deposits form and cause the cell (neuron) to loose viability, resulting in death Molecular Biology 大連理工大學 Conversion Sequence ? Change in structural configuration – folding ? Formation of insoluble aggregates (amyloid plaques) ? Neuronal damage leading to neuronal death ? Death of the host ? Normal = alpha helical configuration ? Abnormal = beta sheet configuration = marker for infectivity Molecular Biology 大連理工大學 Future Focus in Prion Research ? Alzheimer39。 most convenient method – Ultracentrifugation 超離心 – Amino acid sequencing – Xray crystallography x射線晶體學 – Electron microscopy 電子顯微鏡 Molecular Biology 大連理工大學 Macromolecule isolation and characterization ? Nucleic acid – Gene cloning – PCR: polyme