Homologous Chromosome

During zygotene, homologous chromosomes brainstorm to marshal along their unabridged length by a process called synapsis that is necessarily precise.

From: Homo Genes and Genomes , 2012

The Molecular Genetics of Oogenesis

Fan Zhai , ... Jie Qiao , in Human Reproductive and Prenatal Genetics, 2019

Genetic Recombination

Homologous chromosome recombination occurs in meiosis and plays an of import role in genetic diversity, and is also a key determinant in the unique gene profile of an individual. This naturally occurring process has important biological implications in oogenesis, which occurs through Deoxyribonucleic acid repair. The process spans the pachytene, leptotene, and zygotene stages of prophase I and requires the homolog pairing of chromosomes through synapsis complexes.

DNA recombination begins when a topoisomerase SPO11, a type 2 topoisomerase, generates DNA double-strand breaks (DSBs) [34]. DSBs are confined to the specific chromosome regions (hotspots) that contain 13-base of operations pair sequence motifs and are regulated by a number of proteins (e.chiliad., methyl transferases) and histone modifications [eastward.g., histone 3 lysine four trimethylation] [35].

So, MRN (Mre11-Rad50-Nbs1), a heterotrimeric protein complex, performs resection from 5′ to iii′ end of Dna strands at DSB and creates two overhanging 3′ ends. This is followed past unwinding the double-stranded Deoxyribonucleic acid past Sgs1 helicase and slicing the single strand past nucleases. The exchange betwixt 2 homologous chromosomes involves the activeness of the protein complex RPA-Rad51 and the DNA polymerase to create a cross construction called the Holliday junction. Deoxyribonucleic acid is and then repaired either through the DSBR (double-strand break repair) or SDSA (synthesis-dependent strand annealing) pathway that results in crossover and noncrossover products, respectively [36]. A recent unmarried-cell whole-genome sequencing analysis of human polar bodies and oocyte pronuclei from the same individual revealed that the occurrence of crossover in a homo oocyte occurs around 43 times (~   2 per chromosome), which is 1.seven times more frequent than in sperm. In this research, a weak chromatid interference was found. This implies that one crossover between the sis chromatid only slightly reduces the probability for the additional nearby crossover, and indicates that genetic information in the oocyte is being exchanged in dynamic fashion [37]. The recombination probability varies depending on the proximity to the transcription start site (TSS) with underrepresentation of crossovers around TSS [37].

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Synaptonemal Complex☆

J.S. Rufas , in Reference Module in Life Sciences, 2017

Abstruse

Synapsis of homologous chromosomes during meiotic prophase I involves the assembly of the synaptonemal complex (SC), a meiotic-specific structure. The SC was initially described in longitudinal sections of creature pachytene spermatocytes under electron microscopy. This structure has been found in nearly all sexually reproducing organisms, although typically it is absent in males of some species of fruit flies. The SC is a tripartite proteinaceous zipper-like structure that is sequentially bundled during zygotene along the entire length of chromosomes when they are attached to the nuclear envelope and becomes fully assembled in pachytene bivalents (synapsis).

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Recombination | Homologous Recombination in Meiosis

Nancy M. Hollingsworth , Hani Zaher , in Encyclopedia of Biological Chemistry (3rd Edition), 2021

Abstract

During meiosis, homologous chromosomes undergo a reciprocal substitution of DNA to generate crossovers. Meiotic crossovers create physical connections between homologous chromosomes that are necessary for proper segregation at the starting time meiotic division, and also generate new combinations of alleles. The process of meiotic recombination is highly conserved betwixt organisms as diverse as yeast and humans. Recombination is highly regulated during meiosis, such that crossovers occur preferentially betwixt homologs equally opposed to sister chromatids. Furthermore, crossovers are distributed and so that every pair of homologs receives at to the lowest degree ane crossover. The molecular mechanisms of meiotic recombination have been elucidated primarily by research using fungi.

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Genotoxicities and infertility

Tirupapuliyur V. Damodaran , in Reproductive and Developmental Toxicology, 2011

Oocyte chromosome anomalies

Asynapsis of homologous chromosomes at the pachytene stage has been associated with gametogenic failure and infertility, but the cellular mechanisms involved are currently unknown in human meiocytes. In mice, the protein encoded by the breast cancer susceptibility gene Brca1 has been described to directly kinase ATR (ataxia telangiectasia and Rad3 related) to any unpaired Dna at the pachytene stage, where ATR triggers H2AX phosphorylation, resulting in the silencing of those chromosomes. In this written report, the distribution of ATR, BRCA1 and the phosphorylated histone gammaH2AX is assessed by immunofluorescence in human being oocytes and it is found that they localize at unpaired chromosomes at the pachytene phase. Prove is shown to propose that BRCA1, ATR and gammaH2AX in the human may be office of a system such as the one previously described in mice, which signals unsynapsed chromosomes at pachytene and may atomic number 82 to their silencing (Garcia-Cruz et al., 2009). Thioglycolic acid has been shown to inhibit mouse oocyte maturation and affect chromosomal organisation and spindle configuration (Hou et al., 2008). In vivo treatment of trichlorfon resulted in polyploid embryos that might accept arisen from fertilization of oocytes that were either meiotically delayed and still in metaphase I at fertilization or progressed through anaphase II without cytokinesis. In vitro handling of trichorfon resulted in the induction of aneuploidy and polyploidy at the first meiotic sectionalisation and of severe morphological alterations of the 2nd meiotic spindle. Butadiene diepoxide treatment resulted in the induction and transmission of chromosome aberrations in mouse oocytes (Tiveron et al., 1997). Astute exposure of female hamsters to carbendazim (MBC) during meiosis resulted in aneuploid oocytes with subsequent arrest of embryonic cleavage and implantation (Jeffay et al., 1996). Carbendazim (MBC) treatment has been shown to disrupt oocyte spindle function and induce aneuploidy in hamsters exposed during fertilization (meiosis Two) (Zuelke and Perreault, 1995).

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Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency

Maria I. New , ... Tony Yuen , in Genetic Steroid Disorders, 2014

Large-Calibration Cistron Deletion via Diff Crossover

Misalignment of homologous chromosomes during meiosis tin likewise lead to diff crossover resulting in big-scale gene deletions. Crossover tin take place at the C4, CYP21, or TNX genes (Fig. 3A.6). Meiotic unequal crossover results in the transfer of one RCCX module from one chromosome to some other, and the location of the crossover point determines the limerick of the resultant hybrid. Every bit a consequence of the unequal crossover, one bimodular chromosome loses ane RCCX module and becomes monomodular, whereas the other chromosome gains one RCCX module and becomes trimodular (Fig. 3A.vi). Depending on the site of crossover, there are three scenarios regarding inheritance of the agile CYP21A2 cistron. It should be noted that it is oftentimes difficult to pinpoint the exact crossover betoken because of the high sequence similarity between the RCCX modules.

Effigy 3A.6. Large-scale cistron deletion via unequal crossover between two bimodular chromosomes.

Misalignment of a telomeric RCCX module (gray boxes) and a centromeric RCCX module (open boxes) tin can occur between homologous chromosomes during meiosis. Crossover can take place in the C4, CYP21, or TNX genes. The products of crossover between two bimodular chromosomes are one monomodular chromosome with one RCCX module deleted and 1 trimodular chromosome with RCCX module duplicated, resulting in an unequal crossover.

A. Crossover at the C4 genes results in CYP21A1P deletion in one chromosome (Ai) and CYP21A1P duplication in the other chromosome (Aii). Since each of the two chromosomes still carries one copy of the CYP21A2 active gene, diff crossover at C4 does not result in CAH.

B. Crossover at the CYP21 genes results in a monomodular chromosome conveying a CYP21A1P/CYP21A2 bubble (Bi) and a trimodular chromosome conveying CYP21A1P, CYP21A2 genes, and an additional CYP21A2/CYP21A1P chimera (Bii). Offspring inheriting the monomodular chromosome (Bi) volition be at risk for CAH. Offspring inheriting the trimodular chromosome (Bii) will not be affected with CAH because a re-create of the CYP21A2 factor is present.

C. Crossover at the TNX genes results in CYP21A2 deletion in one chromosome (Ci) and CYP21A2 duplication in another chromosome (Cii). Offspring inherited the monomodular chromosome (Ci) will exist at take chances for CAH.
1.

Crossover at C4 results in C4A/C4B and C4B/C4A chimeras, both of which are functional (Fig. 3A.6A). With respect to CYP21, one chromosome loses the CYP21A1P pseudogene but retains the CYP21A2 active gene (Fig. 3A.half-dozenAi), whereas the other chromosome inherits 2 copies of the CYP21A1P pseudogene and ane copy of the CYP21A2 agile factor (Fig. 3A.viAii). Since each of the chromosomes carries one copy of the CYP21A2 gene, crossover at C4 does not event in 21-hydroxylase deficiency.

two.

Crossover at CYP21 genes, on the other mitt, results in one chromosome bearing a CYP21A1P/CYP21A2 chimera (Fig. 3A.6Bi) and the other chromosome bearing a CYP21A2/CYP21A1P chimera and a functional CYP21A2 gene (Fig. 3A.6Bii). Progeny inheriting the CYP21A1P/CYP21A2 bubble (Fig. 3A.6Bi) will exist at risk for 21OHD, equally the chimera carries disease-causing mutations that affect the function of 21-hydroxylase. Based on the location of the crossover, ix CYP21A1P/CYP21A2 chimeras take been classified (CH1–CH9) [67,78–84] (Fig. 3A.vii). CH-iv and CH-9 carry the pseudogene promoter and the P30L mutation. Since these two mutations are rather mild, CH-four and CH-ix chimera types are normally associated with moderate elementary-virilizing CAH. The other seven chimera types are associated with astringent salt-wasting CAH.

FIGURE 3A.7. CYP21A1P/CYP21A2 chimera types.

To date, ix types of CYP21A1P/CYP21A2 bubble (CH1–CH9) with dissimilar junction sites have been identified. These chimeras are ordered here according to the location of the junction sites with respect to the 5' end of the cistron. The first ii chimeras, CH-four and CH-ix, contain mild promoter and P30L mutations and are associated with moderate unproblematic-virilizing CAH. The other 7 chimeras comprise severe mutations and are associated with salt-wasting CAH.

While the CYP21A2/CYP21A1P chimera (Fig. 3A.6Bii) is likely to be non-functional, at that place is a functional CYP21A2 re-create on the same chromosome and then progeny inheriting this chromosome volition not be affected with 21OHD.

iii.

Crossover at TNX genes results in a TNXA/TNXB chimera and a complete deletion of the CYP21A2 factor on one chromosome (Fig. 3A.6Ci), and a TNXB/TNXA chimera and a duplication of CYP21A2 on the other chromosome (Fig. 3A.6Cii). Progeny inheriting the chromosome defective the CYP21A2 gene (Fig. 3A.6Ci) will be at risk for 21OHD.

Whereas unequal crossover between two bimodular chromosomes generates monomodular and trimodular chromosomes, other configurations are as well possible. For case, crossover betwixt a bimodular chromosome and a trimodular chromosome tin generate a monomodular and a quadrimodular product.

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Homology Effects

Sean M. Burgess , in Advances in Genetics, 2002

F. Part of synaptonemal complex in meiotic pairing

While synapsis of homologous chromosomes is a hallmark of meiosis, with some notable exceptions, SC germination does non depend on Dna homology per se. Instead, synapsis betwixt homologous chromosomes appears to occur because of the prior establishment of pairing interactions and the initiation of meiotic recombination (see above and Section Five.B). The genesis of the SC occurs early on in meiosis with the formation of axial elements (AE), which are rodlike structures that develop along the lengths of chromosomes around the time of DSB formation (Padmore et al., 1991). Formation of the tripartite SC construction involves the juxtaposition of the two centric elements from each homolog (now called "lateral elements") connected by a central region (reviewed past Zickler and Kleckner, 1999).

ZIP1 encodes a component of the central element of the SC (Sym and Roeder, 1995). A mutant carrying the zip1 Δ allele was shown to exist lacking for SC germination and, though it initiated recombination at nearly wild-type levels, exhibited a twofold reduction in the level of crossover formation (Sym et al., 1993; Xu et al., 1997). Pairing levels in the zip1 Δ mutant were at wild-blazon levels, consequent with the notion that synapsis does not contribute to either the formation or maintenance of homolog pairing interactions (Nag et al., 1995; Rockmill et al., 1995b). A zip2Δ mutation behaved similarly (Chua and Roeder, 1998). In both zip1 Δ and zip2Δ mutants, homologous chromosomes were aligned along their lengths and connected by interhomolog bridges, also known as interaxis connectors (IC), when visualized by electron microscopy. These bridges are dependent on meiotic recombination, since they were generally absent in zip1 Δdmc1 Δ and zip1Δ hop2Δ double mutants (Rockmill et al., 1995b; Leu et al., 1998). For more details on such bridges in yeast and in other organisms, see Zickler and Kleckner (1999).

In yeast, SC can form in the absenteeism of homologous chromosomes in haploid cells that have been genetically programmed to enter into meiosis (Loidl et al., 1991). These interactions were shown to occur betwixt nonhomologous chromosomes and involved several partner switches. This state of affairs is non different the diploid hop2Δ or mre11S mutants, where SC tin grade between nonhomologous chromosomes as described higher up (Nairz and Klein, 1997; Leu et al., 1998).

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Nondisjunction

B.A. Sullivan , in Brenner's Encyclopedia of Genetics (2d Edition), 2013

Recombination

During MI, homologous chromosomes pair and are held together past synapses. Chiasmata course along the chromosomes at positions where genetic exchange or recombination takes place. These physical connections are important for keeping chromosomes together until they separate in anaphase I. Errors in segregation can occur for several reasons: (one) chromosomes fail to pair or remain paired, (2) recombination does non accept place, (iii) recombination occurs in the incorrect place, or (iv) recombination occurs at too many places on a chromosome. Information technology has been demonstrated in model organisms that mutations in genes involved in synapsis, pairing, and recombination are associated with increased chromosomal NDJ.

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Homology Effects

Gregory B. Gloor , in Advances in Genetics, 2002

three. Chromosome pairing

Proper pairing of homologous chromosomes is the terminal factor that makes of import contributions to the frequency of cistron conversion by double-strand break repair. There is potent evidence for the pairing of multiple sites along homologous chromosomes in both Drosophila and yeast mitotic cells (Aragon-Alcaide and Strunnikov, 2000; Burgess and Kleckner, 1999; Burgess et al., 1999; Fung et al., 1998; Garcia-Bellido and Wandosell, 1978; Golic and Golic, 1996b; Weiner and Kleckner, 1994). This pairing maintains the homologues in proximity to each other, perhaps promoting DNA repair and other processes. The results discussed in a higher place show that homologous chromosomes must be paired both globally and locally for an allelic sequence to be used efficiently as a gene conversion donor (Engels et al., 1990). Strangely, the local pairing requirement is of import but for an allelic donor (Dray et al., 2002). An ectopic donor sequence supports an equivalent factor conversion frequency with or without a large insertion (Nassif et al., 1994). The reason for the difference betwixt allelic and ectopic donors in this regard is unknown, but suggests that allelic sequences are actively recruited as gene conversion donors only if pairing is very tight.

Are the same proteins involved in the global pairing of homologs and in the search for homology that occurs at the broken ends? This question has been addressed only in South. cerevisiae, where the answer depends on the type of cell. Homolog pairing prior to meiosis is augmented by at least some proteins in the RAD52 epistasis grouping. Weiner and Kleckner (1994) plant pregnant disruption of premeiotic chromosome pairing in yeast cells mutant for several of these genes. This disruption occurred prior to double-strand interruption induction by SPO11. They proposed that an initial weak interaction between homologs was established prior to meiosis; this weak interaction was converted to a potent one by strand invasion during the double-strand intermission repair of the SPO11-induced double-strand breaks. In dissimilarity, Burgess et al. (1999) did not detect any issue on homolog pairing in mitotically dividing yeast cells when the homologous recombination pathway was ablated.

Many experiments using Drosophila demonstrate that chromosomes pair in somatic cells throughout the cell cycle, and that local pairing can play an important role in gene regulation (Henikoff and Comai, 1998; Hollick et al., 1997; Marahrens, 1999; Wolffe and Matzke, 1999; Wu and Morris, 1999). The reader is encouraged to investigate the first-class reviews of this topic in this volume. Information technology is exciting to speculate that similar factors are required for chromosome pairing phenomenon such as transvection and for double-strand intermission repair past gene conversion. This convergence can only lead to a deeper agreement of both phenomena. Equally always, farther experimentation volition requite us the answers.

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Interruption–Re-create, Intermission–Bring together

F.W. Stahl , in Brenner's Encyclopedia of Genetics (Second Edition), 2013

Homology-Dependent Break–Join Recombination

In meiosis, homologous chromosomes pair (afterward they accept replicated) and their chromatids bandy segments of DNA (crossing over, Figure i ). An early step in this process of exchange is the introduction of a Deoxyribonucleic acid double-strand break into one of the chromatids ( Figure iii ). The two resulting ends are candy to generate 3′-ended unmarried-stranded Dna, which tin can then invade one of the homologous chromatids. Except in aberrant situations, both of the ends so created interact with the aforementioned chromatid, resulting in the cosmos of a four-stranded intermediate (joint molecule). The resolution of this joint molecule frequently results in exchange that involves no more than Deoxyribonucleic acid synthesis than that required to supersede the Dna that was lost in creation of the invasive three′ single-stranded ends. This modest amount of DNA synthesis (typically simply a few kilobases) is apt to be manifest as gene conversion occurring at the site of the exchange.

Figure 3. Interruption–join recombination of DNA duplexes. (one) Following meiotic DNA duplication, individual chromatids undergo catalyzed double-strand breaks. (2) The two ends and then created are processed to generate single-stranded Deoxyribonucleic acid with 3′ termini. (3) The single stands bind strand-invasion proteins, which promote their invasion of a homologous chromatid. (The vertical black line locates the site of the initiating double-strand pause here and in the following figures.) (4) The invading 3′ terminus primes Dna synthesis that moves and/or expands the D-loop that was created by invasion. (Here and in subsequent figures, newly synthesized strands of DNA are indicated by blocks.) (5) The D-loop anneals with the single-stranded Deoxyribonucleic acid on the other side of the suspension. (half dozen) The annealed three′ terminate primes Dna synthesis. (7) The resulting joint molecule appears to vary with the recombination pathway involved, so is concealed hither to avert an unwieldy discussion. (viii) Resolution of the joint molecule may restore the original chromatids, except for regions of newly synthesized DNA on either side of the initiating break, which are a major source of gene conversion. (9) Resolution of the joint molecule may substitution the chromatid arms, which now bracket the regions of newly synthesized Dna, accounting, in function, for the observed correlation between crossing over and conversion.

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