Lecture 7_II_Mitosis PDF

Associate professor Zanda Daneberga Cell division - mitosis 1 Somatic cell division in eukaryotes ◼ Somatic cell division, gives rise to two genetically identical daughter cells. ◼ Ensure tissue growth, regeneration or asexual (vegetative) repro...

Associate professor Zanda Daneberga Cell division - mitosis 1 Somatic cell division in eukaryotes ◼ Somatic cell division, gives rise to two genetically identical daughter cells. ◼ Ensure tissue growth, regeneration or asexual (vegetative) reproduction. 2 M phase in eukaryotic cell cycle 3 Mitosis ◼ Mitosis (mitos = thread) refers only to the process of nuclear division (karyokinesis). Karyokinesis usually is followed by cytokinesis. ◼ Cytokinesis (kytos = hollow vessel = cell, and kinesis = movement) - the two daughter cells become independent by division of cytoplasm and the rest of organoids. 4 Mitosis - continued ◼ Mitosis – the first step of M phase of the cell cycle. ◼ Cytokinesis - the second step of M phase of the cell cycle. ◼ Both steps partly overlapping. 5 Mitosis - continued ◼ Mitosis consists of five phases: Prophase (pro = before) - the preparative phase. Prometaphase (pro = before, meta = mid) – the transition phase to the next phase. Metaphase (meta = mid) - the middle phase. Anaphase (ana = upper) - the separation phase. Telophase (telos = end) - the final phase. 6 Regulation of mitosis ◼ The key cell cycle (including M phase) regulation proteins - cyclin-dependent kinases (CDKs) - ensure accurate cell cycle progression. ◼ Kinase – an enzyme, adds phosphate groups (PO43−) to other molecules. Kinases can phosphorylate the amino acids serine, threonine, and tyrosine. ◼ CDKs do not have kinase activity unless they are associated with a cyclin proteins. ◼ Concentration of cyclins in the cell fluctuate, CDKs concentration is stable. 7 8 Regulation of mitosis - continued ◼ Plks (Polo-Like kinases) and Aurora kinases control phosphorylation. ◼ Major regulators of centrosome function, spindle assembly, chromosome segregation, and cytokinesis. 9 Regulation of mitosis - continued 10 Prophase 11 Prophase -continued ◼ The chromosomes condense into compact structures. Condensins attach to chromosomes that coil the chromosomes into highly compact forms. H1 histone phosphorylation and attachment of condensins are mediated by Cdk1. H3 histone phosphorylation is mediated by Aurora B kinase. 12  ◼ Cohesin forms rings that hold the sister chromatids together. Source: Soumya Rudra, and Robert V. Skibbens J Cell Sci 2013;126:31-41 13 Prophase - continued ◼ The nuclear membrane breaks down to form a number of small vesicles and the nucleolus disintegrates. Transcription and synthesis stops. ◼ Golgi complex and Endoplasmatic reticulum fragment. ◼ The centrosomes gradually move to take up positions at the poles of the cell. ◼ The beginning of the formation of the mitotic spindle. ◼ The process is mediated by Plks and Aurora A kinases. 14 15  Prometaphase ◼ The chromosomes are completely attached to the mitotic spindle. Spindle fibres are binded to kinetochore. ◼ The chromosomes, led by their centromeres, start migrate to the equatorial plane in the mid-line of the cell. This region of the mitotic spindle is known as the metaphase plate. 16  Metaphase ◼ Chromosomes line up along the metaphase plate. ◼ A key cell cycle checkpoint - the mitotic spindle checkpoint can be activated in the case of mistake in mitotic spindle assembly. ◼ Mediated by APC/C complex (anaphase-promoting complex/cyclosome) and cyclins A and B. 17  Anaphase ◼ Anaphase starts by the initiation of sister chromatid separation. Enzymatic breakdown of cohesins. ◼ The spindle fibres act as tow cables to separate the sister chromatids. ◼ The separated sister chromatids are now referred to as daughter chromosomes. 18 Microtubules in anaphase 19 Microtubules in anaphase ◼ The role of astral microtubules in mitosis is to ensure correct positioning and orientation of the mitotic spindle apparatus based on cell polarity. In anaphase they pull the poles further apart. ◼ Kinetochore microtubules attach to the kinetochore of chromosomes. In anaphase they shorten and draw the chromosomes toward the spindle poles. ◼ Interpolar microtubules extend from the spindle pole across the equator. In anaphase they slide past each other, exerting additional pull on the chromosomes. 20 21  Telophase ◼ The chromosomes arrive at the cell poles. ◼ The mitotic spindle disassembles. ◼ The vesicles that contain fragments of the original nuclear membrane assemble around the two sets of chromosomes. ◼ Phosphatases dephosphorylate the lamins at each end of the cell. This dephosphorylation results in the formation of a new nuclear membrane around each group of chromosomes. 22 Cytokinesis ◼ The physical process that finally splits the parent cell into two identical daughter cells. ◼ The signal for the start of cytokinesis is dephosphorylation of proteins, which are targets of Cdks. 23 Cytokinesis - continued ◼ The cell membrane pinches in at the cell equator, forming a cleft called the cleavage furrow. The position of the furrow depends on the position of the astral and interpolar microtubules during anaphase. The action of a contractile ring of overlapping actin and myosin filaments forms cleavage furrow. 24 Cytokinesis - continued 25 Biological role of mitosis ◼ Growth of the organism. ◼ Repair. ◼ Replaicment. ◼ Asexual reproduction (in plants vegetative multiplication). 26