Chromosome segregation is the process in eukaryotes by which two sister chromatids are formed as a result of DNA replication , or paired homologous chromosomes separate from each other and move to opposite poles of the nucleus . This separation process occurs during both mitosis and meiosis . Chromosome segregation also occurs in prokaryotes . However, unlike eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation is followed by successive replication.
Mitotic Chromatid Isolation
Chromosome separation occurs regularly as a step of cell division during mitosis (see mitosis diagram). As shown in the mitosis diagram, mitosis is preceded by a round of DNA replication, whereby each chromosome makes two copies called chromatids . These chromatids separate from opposite poles, a process facilitated by a protein complex called cohesin . Upon proper separation, a complete set of chromatids ends up in each of the two nuclei, and when cell division is complete, each DNA copy that was formerly called a chromatid is now called a chromosome.
meiosis and chromatid separation
Chromosome separation occurs during meiosis in two distinct phases called anaphase I and anaphase II (see meiosis). A diploid cell has two sets of homologous chromosomes of different paternal origin (e.g. a paternal and a maternal group). During the phase of meiosis labeled “interphase S” in the meiosis diagram, one round of DNA replication occurs, so that each chromosome initially present is now composed of two copies called chromatids ., These chromosomes (paired chromatids) then join with homologous chromosomes (paired chromatids) present in the same nucleus (see meiosis I in meiosis I). The process of alignment of paired homologous chromosomes is called synapsis (see Synapsis ). During synapsis, genetic recombination usually occurs. Some recombination events are crossing over (involving physical exchange between two chromatids), but most recombination events involve information exchange but not physical exchange between two chromatids ( synthesis-dependent strand breaks ). See Annealing (SDSA ). After recombination, the meiosis phase is followed by metaphase I and anaphase I as indicated in the meiosis diagram.
Different pairs of chromosomes separate independently from each other, a process known as “independent classification of non-homologous chromosomes” . As a result of this process each gamete usually contains a mixture of chromosomes from both the original parents. Improper chromosome segregation can result in aneuploid gametes with too few or too many chromosomes .
The second stage at which segregation occurs during meiosis is prophase II (see meiosis). During this phase, segregation occurs by the same process as during mitosis, except that in this case prophase II is not preceded by a single round of DNA replication. Thus the two chromatids containing each chromosome separate into separate nuclei , giving each nucleus a set of chromatids (now called chromosomes) and each nucleus joining a haploid gamete (meiosis II in meiosis II). see subsequent steps). This separation process is called cohesinis also facilitated by Failure of proper segregation during prophase II can also lead to aneuploid gametes. Aneuploid gametes can undergo fertilization to form the aneuploid zygote and hence have serious adverse consequences for the progeny.
Crossovers provide isolation facilities, but are not required
Meiotic chromosomal crossover (CO) recombination facilitates the proper separation of homologous chromosomes . This is because, at the end of meiosis I , CO recombination provides a physical link that holds homologous chromosome pairs together. These relationships have been established by chiasmata , which are cytological manifestations of CO recombination. cohesion between sister chromatidsWith affinity, CO recombination may help ensure the ordered segregation of paired homologous chromosomes to opposite poles. In support of this, a study of aneuploidy in single spermatozoa by whole-genome sequencing found that, on average, human sperm cells with aneuploid autosomes exhibit significantly less crossover than normal cells. [2] After the first chromosome segregation is completed in meiosis I , further chromosome segregation occurs during the second equilateral division of meiosis II . Both the proper initial segregation of chromosomes in prophase I and the next chromosome segregation during equatorial division in meiosis II are required to generate gametes with the correct number of chromosomes.
CO recombinants are produced by a process that involves the formation and resolution of Holliday junction intermediates. As shown in the figure titled “A Current Model of Meiosis”, the formation of meiosis can be initiated by a double-strand break (DSB). The introduction of DSBs into DNA often employs the topoisomerase-like protein SPO11. [3] CO recombination can also be initiated by external sources of DNA damage such as X-radiation, [4] or by internal sources.
There is evidence that CO recombination facilitates chromosome segregation in meiosis. [2] However, other studies indicate that chiasma, while helpful, are not essential for chromosome segregation in meiosis. The budding yeast Saccharomyces cerevisiae is a model organism used for the study of meiosis. cerevisiae defective in CO recombination at the level of Holiday junction resolution were found to efficiently undergo proper chromosome segregation. The cos pathway produces the majority of S. cerevisiae , and possibly in mammals, involves a complex of proteins including the MLH1-MLH3 heterodimer (called MutL gamma). [7] MLH1–MLH3 preferentially bind to Holiday junctions. [8]It is an endonuclease that creates single-strand breaks in supercoiled double-stranded DNA, [8] [9] and promotes the formation of CO recombinases. [10] Deleted double mutants for both MLH3 (major pathway) and MMS4 (which is required for a minor Holiday junction resolution pathway) exhibited a dramatic increase in the number of cells compared to wild-type (6- to 17-fold reduction). showed low crossing over; However spore viability was quite high (62%) and the chromosomal disjunction appeared to be mostly functional. [10]
The MSH4 and MSH5 proteins have a hetero-oligomeric structure (in heterodimer form) in S. cerevisiae and humans. [11] [12] [13] In S. cerevisiae , MSH4 and MSH5 specifically function to facilitate crossover between homologous chromosomes during meiosis. [11] The MSH4/MSH5 complex binds to and stabilizes double Holiday junctions and promotes their resolution into crossover products. An MSH4 hypomorphic (partially functional) mutant of S. cerevisiae showed a 30% genome-wide reduction in crossover number and a large number of meiosis with non-exchange chromosomes. [14]Nevertheless, this mutant gave rise to a spore viability pattern suggesting that the segregation of non-exchange chromosomes occurred efficiently. It thus appears that CO recombination facilitates proper chromosome segregation during meiosis in S. cerevisiae , but is not essential.
The fission yeast Schizosaccharomyces pombe has the ability to separate homologous chromosomes in the absence of meiosis (achiasmate segregation). [15] This ability depends on the microtubule motor dynein which controls the movement of chromosomes at the poles of meiosis.
