The Nucleus I. NUCLEAR ENVELOPE A. Function 1. Separates the interphase nucleoplasm from the surrounding cytoplasm B. Structure 1. It is composed of a lipid bilayer separated by a perinuclear space a) The inner layer is associated with lamins (1) The lamina is composed of three lamin proteins (A, B, and C) (a) The connective tissue autoimmune disease systemic lupus erythematosus is associated with antibody production against lamin B (2) The lamina helps maintain the integrity of the nucleus (a) They disassemble during prophase as the nucleus disintegrates and reforms late in telophase as the nucleus reassembles b) The outer layer is associated with the endoplasmic reticulum (1) In some protein secreting cells, it contains ribosomes and is functionally identical to the rough endoplasmic reticulum 2. Perinuclear space a) The perinuclear space is continuous the cisternae of the endoplasmic reticulum, and proteins can be passed through this connection C. Nuclear pores 1. Function a) To allow for transport of materials into and out of the nucleus (1) For example, ribosomes need to leave the nucleus, while DNA polymerase (made in the cytoplasm) needs to enter the nucleus 2. Structure a) Generally about 3,000 to 4,000 nuclear pores per nucleus (1) This varies with cell type, hormonal cycles, and aging b) The margins of the inner and outer nuclear membranes are continuous around the pore c) The pore can consist in two configuration (1) A closed configuration where a 90 Å pore allows passive diffusion of small molecules (2) An open configuration involves active opening (involving ATP hydrolysis) of the pore to allow transport of larger molecules D. Nuclear membrane during the cell cycle 1. The nuclear envelope, which disintegrates in late prophase, reforms late telophase a) It is dispersed throughout the cytoplasm as small vesicles (100 – 200 nm) during mitosis II.INTERPHASE A. Introduction CHROMOSOMES 1. Interphase is the non-dividing portion of the cell cycle, when the cell is most metabolically active 2. Eukaryotes contain several linear, double-stranded DNA molecules in complex with proteins a) DNA and associated proteins is referred to as chromatin b) DNA is wrapped around 8 core histones (1) Two each of H2a, H2b, H3 and H4 (2) Nucleosomes are DNA wrapped around core histones (3) DNA packed at this level is referred to as euchromatin c) H1 histone can fold nucleosomes into a 30 nm thick solenoid structure B. Euchromatin 1. DNA loosely coiled around histone core proteins 2. Usually not visible 3. DNA may be transcribed C. Heterochromatin 1. Densely packed areas of chromosomes 2. May be constitutive or facultative a) Constitutive heterochromatin (1) Always tightly packed (2) Highly repetitive (3) Not transcribed b) Facultative heterochromatin (1) May uncoil during the cell cycle to become euchromatin III.MITOTIC CHROMOSOMES A. Introduction 1. During cell division, chromosomes are tightly packed and distributed equally to daughter cells a) 50,000 m (50 mm) of DNA is packed to just 5 m B. Changes in chromosomal structure 1. Most euchromatin is packed into heterochromatin 2. Heterochromatin is further folded into loop domain structure a) This further folding requires additional non-histone nuclear proteins C. Chromosome segregation 1. Microtubules of the spindle apparatus binds to and directs chromosome movement IV.SEX CHROMATIN A. In female somatic cells, one copy of the X-chromosome is inactivated 1. In oral mucosa, the deactivated chromosome is associated with the nuclear membrane and is referred to as a Barr body 2. In neutrophils it occupies a small lobe of the nucleus and is referred to as a drumstick 3. In many cells, it occupies the region near nucleolus V. NUCLEOLUS A. Nucleoli are sites of ribosomal RNA (rRNA production) synthesis and the beginning of ribosome assembly 1. Cells actively synthesizing proteins need large numbers of ribosomes, hence the nucleoli are more evident in these cells B. Nucleolar organizing regions 1. Area where many copies of rRNA genes (except 5S rRNA) are being actively transcribed 2. Pale staining area of nucleolus C. Fibrillar and granular region 1. Darker staining regions 2. Ribosomal RNA continues to be processed and begins its association with ribosomal proteins brought in from the cytoplasm 3. The almost finished ribosomes are transported to the cytoplasm, where they become functional