19.01.06 Cell Cycle, Mitosis, Meiosis, Recombination Flashcards
Cell Cycle, Mitosis, Meiosis, Recombination
quiescent/ senescent cells are in which cell cycle phase
G0. Resting phase after cell cycle where cell has stopped dividing
Interphase is composed of which steps
G1, S and G2
What happens in G1
Growth phase. Proteins and RNA synthesised. At G1 checkpoint cell is commited to division and moves into S phase. 9-12 hours.
S phase
DNA synthesis replicates genetic material. Each chromosome consists of two sister chromatids. 6-8 hours
G2
Cell continues to grow. G 2 check point ensures there is enough cytoplasmic material necessary for mitosis and cytokinesis. 2-5 hours
Cell division
M phase. Cell stops growing. First mitosis (nuclear division) then cytokinesis (cell division). Metaphase check point ensures the cell is ready to complete cell division. 1 hour
What is mitosis
Part of the cell cycle where chromosomes in the nucleus are separated into two identical sets of chromosomes contained within their own nucleus.
Steps of mitosis
Prophase, prometaphase, metaphase, anaphase, telophase, cytokinesis.
prophase
Chromosomes condense. Breakdown of nuclear membrane. Spindle fibres appear.
Metaphase
Chromosomes align along metaphase plate
Anaphase
Centromeres divide. Sister chromatids move to opposite poles
Telophase
Nuclear membrane reforms. Chromsomes decondense, spindle fibres disappear.
Cytokinesis
Cytoplasm divides. Parent cell becomes two daughter cells with identical genetic information.
Cell cycle is regulated by
Heterodimeric protein kinases composed of Cyclins and cyclin-dependent kinases (CDKs)
Cyclins
Regulatory subunit
Cyclin- dependent kinases (CDKs)
catalytic subunit of the activated heterodimer which phosphorylates target proteins to orchestrate coordinated entry into the next phase of cell cycle.
Which are constitutively active, cyclins or CDKs?
CDKs are constitutively active
What phase is best for cytogenetic analysis
Metaphase. Cell cycle is stopped using colchicine. Stops spindle fibre apparatus formation.
G1/ s checkpoint involves
Formation of CDK4/ 6-cyclin D. This phosphorylates retinoblastoma protein, relieving inhibition of E2F TF so cyclin E is expressed. Cyclin E then binds to CDK2
g2/M checkpoint involves
p53. DNA damage leads to p53 activation which then inhibits progression through checkpoint. Also CDK1 activation by phosphorylation and dephosphorylation (by cyclin-activating kinase, CAKs) enables binding to cyclin B. This allows transition to M phase.
Metaphase checkpoint
When chromosomes assemble on metaphase plate, anaphase-promoting complex (APC) is activated. This degrades cyclin B/CDK1 cmplex. Separase is then no longer inhibited and can cut spindles. Sister chromatids then separate and enter anaphase.
Meiosis Prophase 1- leptotene step
Nuclear chromatin condense
Meiosis Prophase 1- zygotene step
Maternal and paternal homologous pair to form bivalents, held together by synaptonemal complex.
Meiosis Prophase 1- pachytene step
All homologues are now paired. Chromsomes thicken. Cross over and recombination of material occurs. 60-90 events per cell occur.
Meiosis Prophase 1- diplotene step
Homologues separate (desynapsis) but held together by chiasmata.
Meiosis Prophase 1- diakinesis step
Bivalents more contracted and nuclear envelope breaks down.
Meiosis Prophase 1- detailed steps
leptotene, zygotene, pachytene, diplotene, diakinesis.
Meiosis
specialised cell division that reduces the chromosome number by half. Interphase by two rounds of cell cycle to produce 4 daughter cells, which are not genetically identical to parent cells (unlike mitosis).
Meiosis metphase 1
spindles formed, bivalents aligned
Meiosis anaphase 1
homologous chromosomes drawn apart. Chromatids remain together
Meiosis telophase 1
chromosomes at poles. Haploid daugther cells formed.
Meiosis prophase/metaphase 2
cells pass directly from meiosis 1 to metaphase 2 with no prophase 2. Nuclear envelope breaks down, new spindle formed, chromsomes (consisting of 2 chromatids) align.
Meiosis anaphase 2
separation of centromeres forming 2 haploid cells (4 in total).
Gametogenesis
occurs by meiotic division of diploid gametocytes into various gametes. Oogenesis in females, spermatogenesis in males
Difference between meiosis 1 and 2
1- leads to random independent assortment of chromosome pairs. Random crossover enables genetic recombination.
Meiosis 2- separation of chromatids to a haploid state
Describe spermatogenesis
Spermatogonia differentiate into primary spermatocytes, which undergo meiotic division. After meiosis 2, there are 4 haploid spermatids which then mature into sperm cells.
Describe oogenesis
Primordial germ cells migrate to the forming gonads to form oogonia. These cells proliferate my mitosis before differentiating into primary oocytes. Meiosis 1 begins, reaching meiotic prophase 1 at 8 months gestation. Stay in this state until onset of sexual maturity. SUrge in luteinising hormone (LH) leads to release of oocyte from follicle. After meiosis 2 there is asymtetrical cell division forming a smaller polar body and the ovum.
Non-disjunction
when paired homologues (meiosis 1) or sister chromatids (meiosis 2) fail to separate.
Non-conjugation
homologues fail to pair
how can aneuploidy occur
when sister chromatids separate too early.
When does recombination occur
during prophase 1 stage of meiosis. Homologous chromosomes line up in pairs and swap segments of DNA (crossing over)
Describe process of recombination
- Alignment of 2 homologous DNA strands.
- Breakage of strands (double strand breaks)
- Equal exchange of DNA segments between two strands. Single end invasions resulting in double Holliday junction formation.
- Sealing of resultant DNA molecules with ligases
Consequences of recombination
- NAHR (non allelic homologous recombination)
- Single gene disorder (deletion/dup of single gene), e.g. CF, Rubinstein-taybi (CREBBP, EP300 genes)
- Contiguous gene disorders (several genes deleted/duplicated). e.g. PAX6+WT1 genes in Wilms’ tumour aniridia genitourinary abnormalities.
- segmental aneuploidy syndromes (loss/gain large chromosome regions). Eg. Di George 22q11.2 deletion