Synapsis

Last updated
Synapsis during Meiosis. The circled area is the part where synapsis occurs, where the two chromatids meet before crossing over Synapsis during Meiosis.svg
Synapsis during Meiosis. The circled area is the part where synapsis occurs, where the two chromatids meet before crossing over

Synapsis or Syzygy is the pairing of two chromosomes that occurs during meiosis. It allows matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them. Synapsis takes place during prophase I of meiosis. When homologous chromosomes synapse, their ends are first attached to the nuclear envelope. These end-membrane complexes then migrate, assisted by the extranuclear cytoskeleton, until matching ends have been paired. Then the intervening regions of the chromosome are brought together, and may be connected by a protein-DNA complex called the synaptonemal complex. [1] During synapsis, autosomes are held together by the synaptonemal complex along their whole length, whereas for sex chromosomes, this only takes place at one end of each chromosome. [2]

Contents

This is not to be confused with mitosis. Mitosis also has prophase, but does not ordinarily do pairing of two homologous chromosomes. [3]

When the non-sister chromatids intertwine, segments of chromatids with similar sequence may break apart and be exchanged in a process known as genetic recombination or "crossing-over". This exchange produces a chiasma, a region that is shaped like an X, where the two chromosomes are physically joined. At least one chiasma per chromosome often appears to be necessary to stabilise bivalents along the metaphase plate during separation. The crossover of genetic material also provides a possible defences against 'chromosome killer' mechanisms, by removing the distinction between 'self' and 'non-self' through which such a mechanism could operate. A further consequence of recombinant synapsis is to increase genetic variability within the offspring. Repeated recombination also has the general effect of allowing genes to move independently of each other through the generations, allowing for the independent concentration of beneficial genes and the purging of the detrimental.

Following synapsis, a type of recombination referred to as synthesis dependent strand annealing (SDSA) occurs frequently. SDSA recombination involves information exchange between paired non-sister homologous chromatids, but not physical exchange. SDSA recombination does not cause crossing-over. Both the non-crossover and crossover types of recombination function as processes for repairing DNA damage, particularly double-strand breaks (see Genetic recombination).

The central function of synapsis is therefore the identification of homologues by pairing, an essential step for a successful meiosis. The processes of DNA repair and chiasma formation that take place following synapsis have consequences at many levels, from cellular survival through to impacts upon evolution itself.

Chromosome silencing

In mammals, surveillance mechanisms remove meiotic cells in which synapsis is defective. One such surveillance mechanism is meiotic silencing that involves the transcriptional silencing of genes on asynapsed chromosomes. [4] Any chromosome region, either in males or females, that is asynapsed is subject to meiotic silencing. [5] ATR, BRCA1 and gammaH2AX localize to unsynapsed chromosomes at the pachytene stage of meiosis in human oocytes and this may lead to chromosome silencing. [6] The DNA damage response protein TOPBP1 has also been identified as a crucial factor in meiotic sex chromosome silencing. [4] DNA double-strand breaks appear to be initiation sites for meiotic silencing. [4]

Recombination

In female Drosophila melanogaster fruit flies, meiotic chromosome synapsis occurs in the absence of recombination. [7] Thus synapsis in Drosophila is independent of meiotic recombination, consistent with the view that synapsis is a precondition required for the initiation of meiotic recombination. Meiotic recombination is also unnecessary for homologous chromosome synapsis in the nematode Caenorhabditis elegans . [8]

Related Research Articles

<span class="mw-page-title-main">Meiosis</span> Cell division producing haploid gametes

Meiosis is a special type of cell division of germ cells and apicomplexans in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a zygote, a cell with two copies of each chromosome again.

<span class="mw-page-title-main">Chromosomal crossover</span> Cellular process

Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' non-sister chromatids that results in recombinant chromosomes. It is one of the final phases of genetic recombination, which occurs in the pachytene stage of prophase I of meiosis during a process called synapsis. Synapsis begins before the synaptonemal complex develops and is not completed until near the end of prophase I. Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome.

<span class="mw-page-title-main">Prophase</span> First phase of cell division in both mitosis and meiosis

Prophase is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin reticulum and the disappearance of the nucleolus.

<span class="mw-page-title-main">Genetic recombination</span> Production of offspring with combinations of traits that differ from those found in either parent

Genetic recombination is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryotes, genetic recombination during meiosis can lead to a novel set of genetic information that can be further passed on from parents to offspring. Most recombination occurs naturally and can be classified into two types: (1) interchromosomal recombination, occurring through independent assortment of alleles whose loci are on different but homologous chromosomes ; & (2) intrachromosomal recombination, occurring through crossing over.

<span class="mw-page-title-main">Homologous chromosome</span> Chromosomes that pair in fertilization

A pair of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same loci, where they provide points along each chromosome that enable a pair of chromosomes to align correctly with each other before separating during meiosis. This is the basis for Mendelian inheritance, which characterizes inheritance patterns of genetic material from an organism to its offspring parent developmental cell at the given time and area.

<span class="mw-page-title-main">Heteroduplex</span>

A heteroduplex is a double-stranded (duplex) molecule of nucleic acid originated through the genetic recombination of single complementary strands derived from different sources, such as from different homologous chromosomes or even from different organisms.

<span class="mw-page-title-main">Synaptonemal complex</span> Protein structure

The synaptonemal complex (SC) is a protein structure that forms between homologous chromosomes during meiosis and is thought to mediate synapsis and recombination during prophase I during meiosis in eukaryotes. It is currently thought that the SC functions primarily as a scaffold to allow interacting chromatids to complete their crossover activities.

<span class="mw-page-title-main">Chromomere</span>

A chromomere, also known as an idiomere, is one of the serially aligned beads or granules of a eukaryotic chromosome, resulting from local coiling of a continuous DNA thread. Chromomeres are regions of chromatin that have been compacted through localized contraction. In areas of chromatin with the absence of transcription, condensing of DNA and protein complexes will result in the formation of chromomeres. It is visible on a chromosome during the prophase of meiosis and mitosis. Giant banded (Polytene) chromosomes resulting from the replication of the chromosomes and the synapsis of homologs without cell division is a process called endomitosis. These chromosomes consist of more than 1000 copies of the same chromatid that are aligned and produce alternating dark and light bands when stained. The dark bands are the chromomere.

Zygotene is the second stage of prophase I during meiosis, the specialized cell division that reduces the chromosome number by half to produce haploid gametes. It follows the leptotene stage.

The pachytene stage, also known as pachynema, is the third stage of prophase I during meiosis, the specialized cell division that reduces chromosome number by half to produce haploid gametes. It follows the zygotene stage.

<span class="mw-page-title-main">Sister chromatid exchange</span>

Sister chromatid exchange (SCE) is the exchange of genetic material between two identical sister chromatids.

<span class="mw-page-title-main">Bivalent (genetics)</span>

A bivalent is one pair of chromosomes in a tetrad. A tetrad is the association of a pair of homologous chromosomes physically held together by at least one DNA crossover. This physical attachment allows for alignment and segregation of the homologous chromosomes in the first meiotic division. In most organisms, each replicated chromosome elicits formation of DNA double-strand breaks during the leptotene phase. These breaks are repaired by homologous recombination, that uses the homologous chromosome as a template for repair. The search for the homologous target, helped by numerous proteins collectively referred as the synaptonemal complex, cause the two homologs to pair, between the leptotene and the pachytene phases of meiosis I.

Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.

<span class="mw-page-title-main">TRIP13</span> Protein-coding gene in the species Homo sapiens

TRIP13 is a mammalian gene that encodes the thyroid receptor-interacting protein 13. In budding yeast, the analog for TRIP13 is PCH2. TRIP13 is a member of the AAA+ ATPase family, a family known for mechanical forces derived from ATP hydrolase reactions. The TRIP13 gene has been shown to interact with a variety of proteins and implicated in a few diseases, notably interacting with the ligand binding domain of thyroid hormone receptors, and may play a role in early-stage non-small cell lung cancer. However, recent evidence implicates TRIP13 in various cell cycle phases, including meiosis G2/Prophase and during the Spindle Assembly checkpoint (SAC). Evidence shows regulation to occur through the HORMA domains, including Hop1, Rev7, and Mad2. Of note, Mad2's involvement in the SAC is shown to be affected by TRIP13 Due to TRIP13's role in cell cycle arrest and progression, it may present opportunity as a therapeutic candidate for cancers.

<span class="mw-page-title-main">Chiasma (genetics)</span> Point of contact among homologous chromosomes

In genetics, a chiasma is the point of contact, the physical link, between two (non-sister) chromatids belonging to homologous chromosomes. At a given chiasma, an exchange of genetic material can occur between both chromatids, what is called a chromosomal crossover, but this is much more frequent during meiosis than mitosis. In meiosis, absence of a chiasma generally results in improper chromosomal segregation and aneuploidy.

<span class="mw-page-title-main">Meiotic recombination checkpoint</span>

The meiotic recombination checkpoint monitors meiotic recombination during meiosis, and blocks the entry into metaphase I if recombination is not efficiently processed.

In cell biology, Meiomitosis is an aberrant cellular division pathway that combines normal mitosis pathways with ectopically expressed meiotic machinery resulting in genomic instability.

The leptotene stage, also known as leptonema, is the first of five substages of prophase I during meiosis, the specialized cell division that reduces the chromosome number by half to produce haploid gametes in sexually reproducing organisms.

Achiasmate Meiosis refers to meiosis without chiasmata, which are structures that are necessary for recombination to occur and that usually aid in the segregation of non-sister homologs. The pachytene stage of prophase I typically results in the formation of chiasmata between homologous non-sister chromatids in the tetrad chromosomes that form. The formation of a chiasma is also referred to as crossing over. When two homologous chromatids cross over, they form a chiasma at the point of their intersection. However, it has been found that there are cases where one or more pairs of homologous chromosomes do not form chiasmata during pachynema. Without a chiasma, no recombination between homologs can occur.

Abby F. Dernburg is a professor of Cell and Developmental Biology at the University of California, Berkeley, an Investigator of the Howard Hughes Medical Institute, and a Faculty Senior Scientist at Lawrence Berkeley National Laboratory.

References

  1. Revenkova E, Jessberger R (2006). "Shaping meiotic prophase chromosomes: cohesins and synaptonemal complex proteins". Chromosoma. 115 (3): 235–40. doi:10.1007/s00412-006-0060-x. PMID   16518630. S2CID   28986658.
  2. Page J, de la Fuente R, Gómez R, Calvente A, Viera A, Parra M, Santos J, Berríos S, Fernández-Donoso R, Suja J, Rufas J (2006). "Sex chromosomes, synapsis, and cohesins: a complex affair". Chromosoma. 115 (3): 250–9. doi:10.1007/s00412-006-0059-3. hdl: 10486/13906 . PMID   16544151. S2CID   6569054.
  3. McKee B (2004). "Homologous pairing and chromosome dynamics in meiosis and mitosis". Biochim Biophys Acta. 1677 (1–3): 165–80. doi:10.1016/j.bbaexp.2003.11.017. PMID   15020057.
  4. 1 2 3 ElInati E, Russell HR, Ojarikre OA, Sangrithi M, Hirota T, de Rooij DG, McKinnon PJ, Turner JM (2017). "DNA damage response protein TOPBP1 regulates X chromosome silencing in the mammalian germ line". Proc. Natl. Acad. Sci. U.S.A. 114 (47): 12536–12541. Bibcode:2017PNAS..11412536E. doi: 10.1073/pnas.1712530114 . PMC   5703310 . PMID   29114052.
  5. Turner JM (2015). "Meiotic Silencing in Mammals". Annu. Rev. Genet. 49: 395–412. doi:10.1146/annurev-genet-112414-055145. PMID   26631513.
  6. Garcia-Cruz R, Roig I, Robles P, Scherthan H, Garcia Caldés M (2009). "ATR, BRCA1 and gammaH2AX localize to unsynapsed chromosomes at the pachytene stage in human oocytes". Reprod. Biomed. Online. 18 (1): 37–44. doi: 10.1016/s1472-6483(10)60422-1 . PMID   19146767.
  7. McKim KS, Green-Marroquin BL, Sekelsky JJ, Chin G, Steinberg C, Khodosh R, Hawley RS (1998). "Meiotic synapsis in the absence of recombination". Science. 279 (5352): 876–8. Bibcode:1998Sci...279..876M. CiteSeerX   10.1.1.465.2243 . doi:10.1126/science.279.5352.876. PMID   9452390.
  8. Dernburg AF, McDonald K, Moulder G, Barstead R, Dresser M, Villeneuve AM (1998). "Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis". Cell. 94 (3): 387–98. doi: 10.1016/s0092-8674(00)81481-6 . PMID   9708740.