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Lecture 6
DNA recombination and inactivation
15
Biology
Professional
08/15/2011

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Term
Mitosis
Definition
  • Prophase: chrom. cond, begin formation of mitotic spindle, centrosomes form foci from which MTs radiate and move to poles
  • Prometaphase: nuc membrane breaks up, chroms attach to by kinetochores to MTs of mitotic spindle
  • Metaphase: max condensation at equatorial plane
  • Anaphase: chroms separate, sis chromatids move to opposite poles
  • Telophase: decondense, nuc membrane forms around 2 dghtr nuclei 
Term
Stages of meiosis prophase I
Definition
  1. leptotene: condense, sis chromatids so closely aligned that they cannot be distinguished
  2. zygotene: homolog. chroms. align along length (synapsis), corresponding DNA seq. align, held together by synaptonemal complex
  3. pachytene: chroms much more tightly coiled, tetrads, crossing over
  4. diplotene: synaptonemal complex breaks down, bivalents begin to separate but are held together by chiasmata
  5. diakinesis: maximal condensation
Term
meiosis metaphase I
Definition
  • Nuclear membrane disappears, spindle forms, paired chroms align on equatorial plane 
Term
meiosis Anaphase I and telophase I
Definition
  • disjunction: 2 members of bivalent move apart and their respective centromeres with attached sis chromatids move to opp poles
  • chromosome # is halved 
  • telophase: two haploid sets of chromosomes  grouped at opposite poles
Term
meiosis II
Definition
  • same stages as meiosis I
  • 2 dghtr cells from meiosis I divide to give 4 haploid cells each containing 23 chromosomes 
Term
meiosis in females
Definition
  • begins at 12 wks gestation and arrests at 20 wks in diplotene of meiosis I
  • 1st division completed at ovulation
  • 2nd division completed at fertilization 
Term
2 ways that meiosis contributes to genetic diversity
Definition
  • indep. assortment of maternal and paternal chromosomes at anaphase I
  • recombination of paternal and maternal chromosomes in prophase I (pachytene) 
Term
somatic recombination
Definition
  • recombination in mitosis, very rare
  • fxns in DNA repair 
  • recomb. bet. non-homologous sister chromatids can lead to areas of homozygous recessive state
  • Can be involved in initiating cancer if WT allele codes for tumor suppressor gene 
Term
site-specific recombination
Definition
  • integration of DNA from other species (viral, bacterial) into genome at specific sites 
Term
cohesins (fxn, structure, what about females?)
Definition
  • multi-subunit complex (ring) assembled during S phase and degraded at anaphase forms physical connections bet sis chroms in mitosis + meiosis (sister centromeres)
  • ATP hydrolysis causes openin/closing of ring
  • essential for proper segregation in meiosis
  • sites of chrom recomb and cohesins bet arms lock homologs together until anaphase I
  • degredation of cohesins except at kinetochores allowing homologues to separate
  • cohesin remaining bet sis chromatids and kinetochores is lost allowing sisters to separate at anaphase II
  • in females, S phase is during development and cell division occurs when ovulated - cohesins must fxn for a long time - could be trouble
Term
sinaptonemal complex
Definition
  • forms bet homologous chroms (2 pairs of sis chromatids) during MEIOSIS only
  • mediates chrom pairing + provides scaffold for recomb
  • 2 barrels with a zipper
  • in prophase I: leptotene, SC forms; zygotene, zips; pachytene, locked; diplotene, dissociates but held at recomb sites 
Term
Temporal aspects of recomb and synapsis in meiotic prophase I
Definition
  • Leptotene: programmed DSBs
  • zygotene: homology search bet homologous chroms + initiation of synapsis
  • mid-zygotene thru pachytene: completion of synapsis and repair of DSBs
  • Diplotene: desynapsis of homologous chroms except at chiasmata
  • Diakinesis: condensation of chroms, chiasmata remain, all four chromatids become visible 
Term
MLH1
Definition
  • DNA mismatch repair enzyme involved in formation or processing of recombination events 
Term
Lyon hypothesis (Lyonization, x-inactivation)
Definition
  • in fems, on x chrom is inactivated in each somatic cell
  • dosage compensation (males only have 1 x chrom)
  • occurs ~30 cell stage in development and is fixed - either maternal or paternal x is inactivated in all cells arising from that point
  • randomly determined but fixed
Term
XIST gene
Definition
  • X inactive specific transcript gene: on q arm of x,
  • RNAi is transcribed and binds to x that transcribed it
  • methylation and histone deacetylation attract chromosomal proteins which bind and inactivate
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