quiz 2

• Nucleus

  • largest
  • command center
  • repository of genetic materials
  • molecular machinery of DNA replication and for the synthesis and processing of different types of RNA
• Components of Nucleus

  1. Nuclear Envelope
  2. Chromatin
• Nuclear Envelope

  • selectively permeable membrane separating the nuclear components from the cytoplasmic components
  • double membrane
  • outer membrane - continuous with RER network
  • inner membrane - associated with nuclear lamina; nuclear lamina - stabilizes nuclear envelope
• Nuclear Pore Complexes

  • eightfold symmetrical structure
  • made up of 30 different nuclear proteins
  • nucleoporins or Nups
• Nucleoporins

  • gatekeepers of the nucleus
  • connects outer and inner membrane
• Karyopherin

  • superfamily of nuclear transport receptors
  • also known as importins or exportins
  • assist in the translocation of proteins, RNAs, and ribonuclear particles across the NPC in a Ran GTP hydrolase-dependent process
  • alterations on exportins and importins level may play a crucial role in the development, differentiation of transformation of cells
• Chromatin

  • made of DNA
  • associated proteins involved in the organization and function of DNA
• Components of Chromatin

  • DNA
  • histones
  • DNA binding protein
  • RNA
• Chromatin appear as diffuse mass of fibrous material in normal non dividing cell
• chromatin fibers coil up as separate structures as the cell prepares to divide termed as chromosomes
• Nucleosomes

  • functional unit of DNA and histones
• Chromosomes

  • tightly packed DNA
  • found only during cell division
  • DNA is not being used for macromolecule synthesis
• Chromatin

  • unwound DNA
  • found throughout interphase
  • DNA is used for macromolecule synthesis
• Types of Chromatin

  1. Heterochromatin
  2. Euchromatin
• Heterochromatin

  1. Transcriptionally inactive
  2. Highly packed/condensed form; dark under the microscope
  3. Located at the periphery of the nucleus
  4. Regulate genetic integrity and control gene expression
  5. DNA replicated late in S phase
• Euchromatin

  1. Transcriptionally active
  2. less condensed, loosely packed; light under the microscope
  3. Located at the inner body of the nucleus
  4. Allow gene to form protein
  5. DNA replicated early in S phase
• Heterochromatin

  • closed chromatin conformation; repression
• Euchromatin

  • open chromatin conformation; activation
• Types of Heterochromatin

  1. Constitutive
  2. Facultative
• Constitutive Heterochromatin

  • "not changing"
  • contains satellite DNA
  • stable
  • conserves during all stages of development and in all tissues
  • found in regions of Y chromosomes and some autosomes
  • stained by C bands
• Facultative Heterochromatin

  • "changing"
  • satellite DNA poor
  • enriched in transposon
  • reversible state depending on the stage of development or the cell type examined
  • In X chromosomes, barr body
  • stained by G bands
• Nucleolus

  • non membranous
  • contains primary of RNA
  • site of ribosomal RNA production and assembly
  • Subregions of active nucleolus
  • Fibrillar - site of transcription of ribosomal DNA by RNA polymerase
  • Granular - assembly of the rRNA with the ribosomal proteins
• Nucleostemin

  • p53 binding protein that influences cell differentiation and regulation of cell cycle
  • concentrated in stem cells and tumor cells
• Cell Cycle

  • repeated cycles of macromolecule synthesis (growth) and cell division (mitosis)
  • has four phases
  • G1
  • S
  • G2
  • M
  • regulated by cyclins and cyclin dependent kinases (CDKs)
• Karyotyping is important for many prenatal diagnoses, in which chromosomal analysis of cultured cells from the fetus or amnion can detect certain genetic anomalies.
• nucleolus

  • is a generally spherical
  • highly basophilic sub-domain of nuclei in cells actively engaged in protein synthesis
• Cancer is the common term for all malignant tumors.
• Distinct phase of the cell cycle:

  1. G1 - time gap between mitosis and the beginning of DNA replication
  2. S - period of DNA synthesis
  3. G2 - gap between DNA duplication and the next mitosis
  4. M: prophase, metaphase, anaphase, telophase
• G1 phase

  • longest (8-12 hrs or days, weeks or months)
  • most variable part of the cycle
  • period of active RNA and protein synthesis
  • duplication of organelles
  • cell volume reduced during mitosis returns to its size during this phase
• S phase

  • DNA replication
  • histone synthesis
  • centrosome duplication (6-8hrs)
• G2 phase

  • 2-5hrs
  • completion of centriole replication
  • accumulation of required proteins for mitosis
  • protein synthesis
• G0 phase

  • cells that are not ready for division
  • performs other functions appropriate for that particular cell type
  • some skeletal and most neurons remain in G0 indefinitely and never divide
  • stem cells never enter G0
• Cell Cycle Checkpoints

  • G1 checkpoint
  • Intra S-phase Checkpoint
  • G2/M Checkpoint
  • Mitotic Checkpoint
• Cell Growth Checkpoint (G1 checkpoint)

  • toward end of g phase
  • ensure genome integrity
  • checks if the cell is big enough and has made proper proteins for the synthesis phase
  • if not, cell goes through a resting period (G0)
• DNA Synthesis Checkpoint (Intra S-phase)

  • during synthesis phase
  • checks whether DNA has been replicated correctly
  • if YES, cell continues on to mitosis
• G2/M Checkpoint

  • correct post-replication errors
• Mitosis Checkpoint (Mitotic)

  • during metaphase M
  • checks whether all chromosomes are attached and under bipolar tension
  • if YES, the cell divides and cycle repeats
• SAC checkpoint

  • checks chromosome attachment
• Cyclin-dependent kinases (CDKs)

  • core components of the cell cycle machinery
  • govern transition between phases during cell cycle progression
  • positively regulated by cyclins and negatively by CDK inhibitors
  • Kinases like Aurora, Mps1 and Bub are also critical in chromosome segregation
• Genes involved in cell cycle are frequently mutated in human cancer and deregulated CDK activity represents a hallmark of malignancy