Chapter 1.1-1.2

1.1: Composition of nucleic acids and polypeptides

  • Purines have two interlocked rings.

    • Adenine

    • Guanine

  • Pyrimidines have a single ring.

    • Cytosine

    • Thyine

    • Uracil

  • In nucleic acids, each base is covalently attached to the sugar by an N-glycosidic bond.

    • A sugar with an attached base is called a nucleoside

    • A nucleoside with a phosphate group is the basic repeat unit of a DNA strand, and called a nucleotide.

1.2

  • In DNA, chemical modification is limited to methylation of bases.

    • These are epigenetic marks that serve as a reversible switch to regulate transcriptional activity.

  • The machinery for DNA replication relies on a variety of proteins and RNA primers, and has been highly conserved during evolution.

    • Topoisomerase: Start the process of DNA unwinding by breaking a single DNA strand

    • Helicase: unwind the double helix at the replication fork (after supercoiling has been eliminated).

    • Single strand DNA binding proteins: maintain the stability of the replication fork as single stranded DNA is vulnerable to enzymatic attack.

    • Primase: attach a small complementary RNA sequence (primer) to single stranded DNA at the replication fork. Provides the 3’ hydroxyl group needed by DNA pol to begin synthesis.

    • DNA polymerase: Synthesize DNA strands.

    • DNA ligase: seal nicks that remain in newly synthesized DNA after the RNA primers are removed and the small gaps are filled by DNA pol.

2.4

  • Nucleosome organization is a key step in compacting DNA

    • Binding of basic histone proteins causes the double helix to undergo a first level of compaction.

    • Key structure of a nucleosome: DNA is wrapped in almost two turns around eight core histone proteins, two of H2A H2B H3, and H4.

    • H1 is bound to linker DNA outside of the histone.

    • It is the pattern of the open and condensed euchromatin regions across chromosomes that primarily determines which genes are expressed and which are switched off, thereby defining the identity of a cell.

  • The two types of heterochromatin

    • Most heterochromatin is described as constitutive heterochromatin because it is permanently, irreversibly condensed. It is gene-poor.

    • Facultative heterochromatin has a condensed structure that can be reversed and can be rich in genes.

10.1

  • Nucleosome positioning and chromatin remodeling complexes

    • Nucleosome positioning can be altered by chromatin remodeling complexes, which are large ATP powered multiprotein machines that physically shuffle nucleosomes along the DNA.

    • Mutations in components of remodeling complexes are important in cancer and congenital conditions such a the Coffin-Siris group of syndromes.

10.2

  • Nucleosomes have a positive charge that attracts them to the negatively charged DNA.