Meiosis and Its Check Points Presented by Stella Lakra 23310021 Cell and Molecular Biology CBIO618
Meiosis Introduction Also known as reduction division, of a germ cell involving two fission of nucleus and giving rise to four gametes , or sex cells, each possessing half the number of the chromosomes of original cells. At this stage the major difference from mitosis is that in meiosis the two chromatids making up each chromosome remain together, so that the whole chromosome are separated from their homologous partner. Cell division occurs followed by a second division that resembles mitosis more closely in which it separates the two chromatids of each remaining chromosome. Finally at the end of meiosis each mature gamete receives only one copy of each gene instead of two copies.
Prophase I Here the DNA strands thickens into chromosomes. Homologus, or like, chromosomes begin to approach each other. Then the homologus chromosome pair to form bivalent. The centrioles divide and move to opposite poles of the cell. The bivalent duplicates to form tetrads, or four chromatid groups. The nuclear membrane disintegrates and crossing over (recombination) occurs.
Leptotene The first phase of division I of meiosis, in which the paired duplicated homologous chromosomes condense and become visible in the light microscope . Zygotene Second stage of division I of meiosis, in which the synaptonemal complex begins to form between the two sets of sister chromatids in each bivalent chromosome . Pachytene Third stage of division I of meiosis, in which synapsis In genetic recombination, the initial formation of base pairs between complementary DNA strands in different DNA molecules that occurs at sites of crossing-over between chromosomes. In meiosis, the pairing of maternal and paternal copies of a chromosome as they become attached to each other along their length is complete .
Diplotene: In this phase, homologs tend to be as far apart as possible except at the position of chiasmata, moreover in each interchiasm region the plane of homologous pair is perpendicular to plane in adjacent interchiasm region. Steric constrain due to convergence of “flat chromosome” at chiasmata, chromosome stiffness, and/ or “repulsion” forces could be responsible .
Diakinesis : Homologs coil into higher order gyres. In general, pure of two homologs are phased with one another and are of opposite helical headedness. The latter feature may arise during compaction, enforced by the presence of previously established interhomology crossover.
Metaphase I The tetrad attach to the spindle fibres at their centromeres, line up at the middle of the cell.
Anaphase I In early phase the tetrads separate and the paired chromatids move along the spindle to their respective centrioles. In late anaphase the chromatids have almost reached the spindle poles. The cell membrane begins to construct. At this phase highly condensed chromatid cores converge at chiasmata, large number of such convergence could preclude maximal compaction.
Telophase I In this phase the nuclear membrane encloses the separated chromatids. The cell membrane completes its construction. After which the first meiotic division ends and formation of two cells, each with the same number of chromatids as the parent cells.
Prophase II It begins just after first meiotic division ends In this phase the homologous chromatids do not duplicate but merely separates.
Metaphase II The chromatids line up at mid-cell. The centrioles and asters are at the poles, and a spindle has formed. Anaphase II The now-separated chromatids approach their respective poles. The cell membranes begin to constrict . Telophase II At the end of Telophase the nuclear membrane reappears and the formation of four daughter cells, each carrying half the number of chromosome of parent cell takes place.
Checkpoints in Meiosis The meiotic checkpoint network creates a web of dependencies to promote sequential progression of meiotic events (A), or prevent meiotic progression in the face of defective repair or synapsis (B).
DSB dependent Pathway The abrupt onset of M- Cdk in late prophase I depends on the positive transcription regulation feedback loop consisting of Ime2, Ndt80 and Cdk / cyclin complex. However the activation of M- Cdk is controlled by the general phosphorylation switch Wee1 / Cdc25 . Wee1 activity is high in early prophase I and the accumulation of Cdc25 activates M- Cdk by direct phosphorylation and marking Wee1 to be degraded. Meiotic recombination may begin with a double-strand break, either induced by Spo11 [2] or by other endogenous or exogenous causes of DNA damage. These DNA breaks must be repaired before metaphase I. and these DSBs must be repaired before metaphase I. The cell monitor these DSBs via ATM pathway, in which Cdc25 is suppressed when DSB lesion is detected. This pathway is the same as classical DNA damage response and is the part we know the best in meiotic recombination checkpoint.
DSB independent Pathway The DSB-independent pathway was proposed when people studied spo11 mutant cells in some species and found that these Spo11 cells could not process to metaphase I even in the absence of DSB. [3] The direct purpose of these DSBs is to help with the condensation of chromosomes. Even though the initial homolog paring in early leptotene is just random interactions, the further progression into presynaptic alignment depends on the formation of double strand breaks and single strand transfer complexes. [1] [4] Therefore the unsynapsed chromosomes in Spo11 cells can be a target of checkpoint. An AAA–adenosine triphosphatase (AAA-ATPase) was found to be essential in this pathway. [5] but the mechanism is not yet clear.
Some other studies also drew sex body formation into attention, and the signaling could be either structure based or transcription regulation such as meiotic sex chromosome inactivation . [6] [7] Under this cascade, failure to synapse will maintain the gene expression from sex chromosomes and some products may inhibit cell cycle progression. Meiotic sex chromosome inactivation only happens in male, which may partially be the reason why only Spo11 mutant spermatocytes but not oocytes fail to transition from prophase I to metaphase I. [3] [8] However the asynapsis does not happen only within sex chromosomes, and such transcription regulation was suspended until it was further expanded to all the chromosomes as meiotic silencing of unsynapsed chromatin , [9] but the effector gene is not found yet.
References :- Nancy Kleckner , “Review on Meiosis : How it Works ?”. Proc. Natl. Aca . Sci. USA Vol. 93, pp. 8167-8174, August 1996 . Britanica Barchi M, Mahadevaiah S, Di Giacomo M, Baudat F, de Rooij DG, Burgoyne PS, et al. (August 2005). "Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage“. Malik SB, Pightling AW, Stefaniak LM, Schurko AM, Logsdon JM (August 2007). Hahn MW (ed.). "An expanded inventory of conserved meiotic genes provides evidence for sex in Trichomonas vaginalis . Morgan DO (2007). "Chapter 9: Meitosis ". The Cell Cycle: Principles of Control . London: New Science Press Ltd. ISBN 978-0-87893-508-6