Cell Cycle Lecture Notes PDF

The Cell Cycle Dr. Gemma Barron [email protected] This Photo by Unknown Author is licensed under CC BY-SA Today’s Learning Outcomes At the end of today’s class, you should be able to: Identify the basic concepts relating to the genetic material contained with...

The Cell Cycle Dr. Gemma Barron [email protected] This Photo by Unknown Author is licensed under CC BY-SA Today’s Learning Outcomes At the end of today’s class, you should be able to: Identify the basic concepts relating to the genetic material contained within cells: Genome, chromosomes, genes and many others. Define and explain mitosis recognising function and products. This Photo by Unknown Author is licensed under CC BY-SA Define and explain meiosis recognising function and products. Why is this important? Inheritance Will a disease-causing allele or variant of a gene be passes on? Will an error in meiosis result in an extra chromosome being inherited? Disease development, e.g., cancer Development of congenital disorders Genes and chromosomes Genes and chromosomes 1.8m DNA per cell Condensed into 46 chromosomes (23 pairs) each containing many genes, DNA wound around histone ‘bobbins’  nucleosomes. Nucleosomes coiled into fibres. DNA + protein = chromatin  Chromosomes This is also a This is a chromosome! chromosome! (following DNA replication in S/G2 Short (p) arm phase) centromere Chromatid How many chromosomes? Count the centromeres. Long (q) arm Two chromatids (sisters) Chromosomes: Human karyotype Each somatic cell contains 46 chromosomes. 22 homologous pairs (1 from each parent) Sex chromosomes: XY or XX In the Karyotype you can see pairs of chromosomes. Each chromosome has a single chromatid. Prior to cell division, the DNA in the chromosome will be replicated to form two sister chromatids. http://www.genome.gov/glossary/resources/karyotype.pdf, Public Doma 1 ‘set’ = ’n’; normal somatic cells ‘2n’ (diploid) Cell Division: Mitosis and Meiosis Mitosis: 2 daughter cells are produced that are genetically identical to the parent cell. Asexual reproduction Growth Repair Tumours Meiosis: 4 daughter cells are produced (each containing half the number of chromosomes) that are genetically different from each other and from the parent cell. Cell cycle Mitosis is just one part of the cell cycle. In the mitotic phase of the cell cycle, replicated chromosomes are separated into two daughter nuclei. This is followed by cytokinesis, the division of the cytoplasm that results in two individual cells. The mitotic (M) phase of the cell cycle alternates with the much longer interphase: G1, S, G2.  Stages G1 (“Gap”) and G0 Duplication of cell contents (except DNA) Not genetic material Restriction point(s?) Determines: progression or G0 G0: Quiescence, senescence, or temporary ‘repair stop’ P53 and apoptosis  Stages S (“Synthesis”) and G2 S: Chromosomes duplicated to give sister chromatids G2: Busy synthetic phase Cell making lots of proteins for cell division Another checkpoint here Stage M Prophase and Prometaphase Prophase: chromosomes condense and the spindle forms. Prometaphase: nuclear envelope breaks down, microtubules attach to kinetochores (proteins on the centromere of the chromosome).  Metaphase, Anaphase and Telophase Ali Zifan, Wikimedia Commons s file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license. Oncogenes and Tumour Suppressor Genes Tumour Suppressor Genes… BRCA1 is involved in repairing double-strand breaks in DNA, and in mismatch repair. BRCA1 is involved in regulation of the mitotic spindle checkpoint. Failure – damaged cells divide Can give rise to cancer Therapeutic Targeting? Inhibitors of oncogenes or oncogene-associated pathways. Restoring the function of tumour suppressor genes (e.g. rescuing wild-type function, targeting regulators of the gene, targeting downstream signalling pathways of the protein) Countering the effects of mutated BRCA1/2 When there are mutations in BRCA1/2, a back-up, error- prone DNA repair process is used instead, allowing cells with mutations in their DNA to progress through the cell cycle. This error-prone process uses DNA polymerase theta (Polθ). ART558 is a small molecule inhibitor of Polθ. Without the ability to repair DNA, BRAC1/2-mutant tumour cells die. If gametes underwent mitosis… … the fusion of gametes would produce offspring with four sets of chromosomes after one generation, eight sets after two generations etc. Obviously, for humans this is unviable, hence meiosis occurs where the chromosome number is halved. Fertilisation restores the diploid condition in the zygote (n + n = 2n) Diploid as opposed to Haploid Gametes Somatic cells cell = cell = n 2n Meiosis Similar processes involved 2 very different outcomes 4 haploid cells Far from identical Genetic variation Starting point: gametogonium (2n) Task: Compare and contrast mitosis and meiosis Meiosis 1 Meiosis 2 The end result is 4 haploid gametes that are all genetically different Summary You need to be able to identify and describe the basic concepts of genetic material. You also need to define and explain (i) mitosis and (ii) meiosis recognising the role and what is produced. To help you revise this topic, you could make notes on similarities and differences. Ideas for further reading and discussion will be uploaded to the PL1003 Moodle page.