oceg + stem cell

• Eukaryotic chromosome


  Single linear DNA double helix, which undergo multiple levels of packaging, along with large amount of proteins

  
• The total length of the 46 DNA molecules in a human cell, when extended, measure up to 2-meters, 20 thousand times longer than the cell diameter
• Packaging of DNA into chromatin / chromosome


  • Achieved by the formation of highly organized complex of DNA and proteins, which is further extensively folded into chromatin and eventually chromosome

  
• Levels of DNA packaging

  • Nucleosomes
  • 30-nm chromatin fiber / solenoid
  • Looped domains

  
• Nucleosome


  DNA-histone complex / nucleoprotein complex with the appearance of 'bead-on-a-string'

  
• Binding of DNA to histones

  Negatively charged DNA binds to positively charged histones by ionic bonds
• Each nucleosome bead consists of DNA wound around a protein core consisting of eight histone molecules (octameric histones)

  
• Two molecules each of four different types of histones – H2A, H2B, H3 & H4
• Histone H1


  Attaches to linker DNA near the nucleosome, promoting interaction between adjacent nucleosomes and allowing chromatin to undergo the next level of packaging into a 30-nm fiber

  
• 30-nm chromatin fiber / solenoid

  String of nucleosome beads coil around itself into a higher order helix with the aid of the H1 histone

  
• There are 6 nucleosomes per turn of the helix of the solenoid

  
• Looped domains


  The 30-nm chromatin fiber attaches to multiple locations on a chromosome scaffold in a series of looped domains to form 300-nm fiber

  
• The chromosome scaffold is made of non–histone proteins that help the compaction of 30-nm chromatin into metaphase chromosome

  
• Heterochromatin


  Highly condensed/compact chromatin that makes up ~10% of an interphase chromosome, genes within are transcriptionally inactive

  
• Euchromatin


  More diffused/less compacted chromatin, transcriptionally active as DNA is accessible to transcription machinery

  
• The chromosome is a dynamic structure that is condensed, loosened, modified and remodelled as necessary for various cell processes

  
• Chemical modifications of histones affect the state of chromatin condensation and also have multiple effects on gene activity
• Genome


  The complete DNA sequence of an organism/species, including both coding and non-coding sequences

  
• Coding DNA sequences


  Regions of DNA known as genes that are transcribed and/or translated

  
• Gene


  A discrete unit of hereditary information consisting of specific nucleotide sequence in DNA (or RNA in some viruses) which codes for RNA or a specific sequence of amino acids in a protein

  
• Genes make up only a small portion of the eukaryotic genome (about 1.5% in humans) as most of the DNA does not encode protein

  
• Gene families


  Groups of identical or similar genes
• More than half the genome's coding DNA occur in multiple copies, which could be clustered (grouped together) or dispersed in the genome

  
• Multi-gene families


  • Globin gene families (-globin and -globin)

  
• Non-coding DNA sequences


  Sequences of the DNA molecule that do not code for any protein or RNA

  
• Types of non-coding sequences


  • Centromeres
  • Telomeres
  • Introns
  • Regulatory sequences associated with genes

  
• Centromere

  Non-coding, repetitive DNA sequences that are the site where kinetochore proteins attach and where cohesin proteins bind sister chromatids together

  
• Telomeres


  Short, repeating, non-coding DNA sequence found at the two ends of the DNA / chromosome

  
• The telomeres of humans consist of a repeat of six nucleotide sequences, 5' TTAGGG 3'

  
• End replication problem


  The shortening of DNA after each round of replication due to the inability of DNA polymerase to fully replicate the lagging strand
• The shortening of telomeric DNA is observed in most dividing somatic cells and in cells cultured in the laboratory
• Telomerase


  Ribonucleoprotein enzyme that catalyses the lengthening of telomeres

  
• Telomerase has a short RNA sequence which provides a template to guide the insertion of the telomere repeat TTAGGG

  
• Telomeres


  DNA sequences at the ends of chromosomes that become shorter in older individuals

  
• Telomeres


  • They have a limited number of times (~40-60 times; known as the Hayflick limit) that each cell can divide before essential genes are lost
  • When shortened to a 'critical length', they undergo cellular senescence (cell division completely stops) and apoptosis (programmed cell death)

  
• Telomerase


  An enzyme that can restore shortened telomeres
• Prokaryotes do not face the same end replication problem as eukaryotes
• Telomerase


  A ribonucleoprotein - a complex of RNA and proteins

  
• Telomerase RNA


  Provides an AAUCCC template to guide the insertion of the telomere repeat TTAGGG

  
• Telomerase protein


  A reverse transcriptase that synthesizes DNA from its RNA template