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BIOB11H3 (13)
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Chapter 12

Chapter 12 notes

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Biological Sciences
Dan Riggs

Chapter 12 The nucleus contains chromosomes (condensed into chromatin = chromosomes + proteins), nucleoli, nucleoplasm, and nuclear matrix. The inner surface is bound by integral membrane proteins that are connected to filamentous meshwork called nuclear lamina (made up of lamins). A nuclear pore complex (NPC) has an octagonal symmetry - contains only about 30 different proteins, called nucleoporins (at least 8 copies). Low-molecular-weight solutes may penetrate the nuclear pores by simple diffusion, whereas proteins and RNAs have to pass throught he central channel with the help of special transport systems. The nuclear localization signal (NLS) is a strech of positively charged amino acids in the C-terminus that enables proteins to pass through the nuclear pores. Mobile transport receptors include importins (move macromolecules from cytoplasm into nucleus) and exportins (opposite direction). Importing: - NLS-containing cargo bind to a heterodimeric, soluble NLS receptor called importin a/b in the cytoplasm - Importin escorts the protein cargo to nucleus, where it docks with the cytoplasmic filaments that extend from the outer NPC ring www.notesolution.com - It moves through the nuclear pore by hopping from one binding site on the NPC to the next - Ran-GTP binds to importin a and causes the cargos disassembly - Ran-GTP with importin a move outside nucleus - Ran-GTP is hydrolyzed and importin a is released - importin b moves outside with the help of exportin There is high concentration of Ran-GTP inside nucleus and low outside. RCC1 in the nucleus converts Ran-GDP into Ran-GTP and RanGAP1 in the cytoplasm converts Ran-GTP into Ran-GDP to maintain gradient, which is important for nuclear transport. Ran-GTP induces disassembly of imported materials and the assembly of materials to be exported. Proteins exported from the nucleus contain amino acid sequences (nuclear export signals NES). - Introns are spliced out - Exons join and exon junction complex (EJC) is added to where the exons meet - TAP binds to Aly (one of the proteins of EJC) making it capable of being transported through the NPC - After export, Aly and TAP are released - then EJCs are released upon translation _____________________________________________________________________________ ____________________________________ www.notesolution.com An average human cell contains about 6.4 billion base pairs of DNA divided among 46 chromosomes. 2 m of DNA packaged into 10 um nucleus. How? Histones are group of proteins with high content of arginine and lysine. They interact with the DNA backbone, thats why they are highly conserved among species. Kornberg proposed that DNA and histones are organized into repeating subunits, called nucleosomes. Each nucleosome contains a nucleosome core particle (146 DNA bp) wrapped twice around a disk-shaped complex of 8 histone molecules (2 copies of H2A, H2B, H3, and H4). H1 is a linker histones, binds to part of the linker DNA. Histones and DNA interact at places where the minor groove faces the histones. Packing ratio of DNA of nucleosomes is approximately 7:1. Nucleosomes are 10 nm. Electron micrograph shows 30 nm chromatin fibers - nucleosomes are assembled together to increase compactedness 6 fold. Removing H1 results in the less compact beads-on-a-string structure. H1 and the tails of histone subunits (e.g. N-terminal tail of H4) mediate the higher folding nucleosomes. Addition of methyl groups on H3 core histones can promote chromatin compaction and transcription silencing. Acetylation of lysine has the opposite effect, making DNA more accessible to interacting proteins that promote transcriptional activities. www.notesolution.com The 30-nm chromatin fibers gather into a series of large supercoiled loops that may be compacted into thicker fibers. DNA loops are tethered at their ends to proteins like type II topoisomerase that regulate the degree of DNA supercoiling. Mitotic chromosomes are extremely compact: packing ratio is 10,000:1. - Euchromatin are chromatins that return to dispersed (dissolved) state after mitosis. - Heterochromatin stay in compact state even during interphase (after mitosis). It has little transcription activity. - Constitutive heterochromatin remains in compact state in all cells at all times -> permanently silenced DNA. Found in telomere and centromere regions. Consists primarily of repeated regions and contains few genes. - Facultative heterochromatin is specifically inactivated during certain phases of an organisms life or in certain cells. e.g. only one X chromosome is transcriptionally active in girls (the other remains condensed, called Barr body) but X and Y chromosmes are active in boys. Note: the position effect is when transposons become transcriptionally silent when they move to a place near constitutive heterochromatin. Their influence spread outward a certain distance - blocked by boundary elements. Lyon proposed that adult females are genetic mosaic. She based this on the fact that heterochromatization occurs earily in embryonic www.notesolution.com
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