Genetics 10

• Viruses are small infectious particles that contain nucleic acid surrounded by capsid of proteins.
• Linear or Circular
• Relatively Small
• RNA or DNA (not both) 

• Sheath
• Base Plate
• Tail Fibers

• No assembly required: Nucleic acid and capsiid proteins spontaneously bind to each other to form a mature virus.
• Assembly required: requires the involvement of non- capsid proteins to direct the proper assembly of the virus.

• Scaffolding proteins: catalyze assembly process.
• Protease-like proteins: cleave viral capsid proteins into smaller units which allows for correct assemblages. 

• Highly compacted.
• Occurs in the nucleoid.
• Can be multi copied. 
• Millions of base pairs long.
• Contains a few thousand genes. 

• Structural gene sequences: encode proteins.
• Intergenic regions: nontranscribed regions.
• Origin of replication: unique DNA sequence at which replication is initiated.
• Repetitive sequences: (<10bp) found in multiple copies interspersed within the intergenic regions. 

• Underwinding (left handed) = negative supercoiling (fewer turns)
• Overwinding (right handed) = positive supercoiling (more turns) 

Strands that only differ with regards to supercoiling.

• Reduction of size.
• Promotes replication and transcription of these small regions. 

• DNA gyrase (toposimoerase II) : induces negative supercoiling.
• Topoisomerase I : Relax negative supercoils. 

• Origin of replication: Multiple, which are essential to replication.
• Centromeres : Essential to proper segregation of chromosomes during mitosis & meiosis.
• Telomeres : Prevents sticky ends, protect chromosomes from digestion, prevents shortening in DNA replication. 

1-100kbp

• Sequences only found one or a few times within a genome.
• This includes the vast majority of proteins encoded for by genes present in one or a few copies.
• 40% of the human genome (some genes are only used in portions of our body because tissues only use certain genes their entire lifespan.) 

• Those found a few hundred to several thousand times in the genome.
• Multiple copies of the same gene.
• Transposable elements. 

• Those found 10k to 1mil times in the genome.
• Relatively short. (few to several 100 bp)
• Repeats can also occur as tandem repeats (often found in centromeric or telomeric regions) 

• The faster DNA renatures the less complex (more highly repetitive) it must be.
• The slower DNA renatures the more complex (more unique) it has to be. 

• Two copies of each of the four different histone subunits.
• DNA makes 1.65 negative superhelical turns around the octamer.
• Requires 146bp of DNA per octamer. 

146 nucleotide base pairs wrapped around an octamer.

• It connects nucleosomes.
• Varies in length from 20-100bp. 

• H2A
• H2B
• H3
• H4

• H1
• binds to one side of the nucleosome and to the linker region. 

Histones contain large numbers of positively charge lysine and arginine amino acids. The electrostatic & hydrogen bonding between the histones and phosphate backbone keep them bound.

Formation of a nucleosome.

• 30 nm fiber.
• Nucleosome (6-8) associate with each other to form a more compacted structure.
• DNA enzymes can not transcribe in this state. 

Formation of Radial loop domains.

30nm fibers interact with a filamentous network of proteins in the nucleus to form 10nm loops lining the inner membrane and nucleus.

• Matrix attached regions
• Scaffold- arrached regions
• Sequences which bind specific proteins in the nuclear matrix causing loops to form. 
• Up to 200kbp

• Regulation of gene expression.
• Maintain chromosome territories ( discrete, non-overlapping regions)

• Euchromatin is less condensed regions capable of gene transcription.
• Heterochromatin is tightly compacted regions of chromosome (highly repetitive DNA sequences) generally transcriptionally inactive. 

• Constitutive : always heterochromatic and permanently inactive with regards to transcription. Highly repetitive DNA.
• Facultative : ability to convert between heterochromatin and euchromatin. (barr body)

Histones can be reversibly modified at specific sites in their N-terminal tails protruding from the nucleosome core. Important in the role of altering DNA accessibility and chromatin structure. Amino acids on the tail can be acetylated, methylater, and phosphorylated.

• The enzyme HAT ( Histone acetyltransferase ) acetylates histones so that transcription can more readily occur.
• The enzyme HDAC ( Histone Deacetylase ) deacetylates histones to repress transcription. 

Most chromosomal DNA is in a 300nm configuration (corresponds to euchromatin). Except for the centromeres which are heterochromaticaly compacted to a diameter of 700nm.

Sister chromatids are entirely heterochromatic and have a diameter of 1.4k nm, but are short in length.

• Proteins (along with topisomerases) that use ATP to catalyze changes in chromosome structure.
• Dimers connected at the hinge region.
• Fold, Tether, and manipulate DNA. 

• Condensing
• Cohesin 

• Promotes greater compaction of the raidial loops.
• Regulated differently. 

• Type 1: Located in cytoplasm during interphase. Gains access to chromosomes only after nuclear envelope breaks down.
• Type 2: Located in cell nucleus during interphase. Involved early chromosome condensation of prophase.

• Promotes the binding between sister chromatids along their entire lengths from S phase untile middle of prophase.
• Remains at centromeric regions until anaphase at which time is rapidly degraded by a protease called Separase (hydrolyzed subunit called "Securin").