Auswahl der wissenschaftlichen Literatur zum Thema „Mitosis/meiosis transition“

Meiosis was existing already in the last eukaryotic common ancestor (LECA). During evolution and transition from the first eukaryotic ancestor to LECA, a whole complex of genes was formed in the genome of the latter (about 300 genes), which provided the process of meiotic division. This is only a few percent of the genome, but these genes significantly changed the course of cell division, and meiosis arose. The paper describes the features of meiosis and possible ways of its formation.

Abstract Genetic evidence suggests that the mei-1 locus of Caenorhabditis elegans encodes a maternal product required for female meiosis. However, a dominant gain-of-function allele, mei-1(ct46), can support normal meiosis but causes defects in subsequent mitotic spindles. Previously identified intragenic suppressors of ct46 lack functional mei-1 activity; null alleles suppress only in cis but other alleles arise frequently and suppress both in cis and in trans. Using a different screen for suppressors of the dominant ct46 defect, the present study describes another type of intragenic mutation that also arises at high frequency. These latter alleles appear to have reduced meiotic activity and retain a weakened dominant effect. Characterization of these alleles in trans-heterozygous combinations with previously identified mei-1 alleles has enabled us to define more clearly the role of the mei-1 gene product during normal embryogenesis. We propose that a certain level of mei-1 activity is required for meiosis but must be eliminated prior to mitosis. The dominant mutation causes mei-1 activity to function at mitosis; intragenic trans-suppressors act in an antimorphic manner to inactivate multimeric mei-1 complexes. We propose that inactivation of meiosis-specific functions may be an essential precondition of mitosis; failure to eliminate such functions may allow ectopic meiotic activity during mitosis and cause embryonic lethality.

The kinase cyclin B–Cdk1 complex is a master regulator of M-phase in both mitosis and meiosis. At the G2/M transition, cyclin B–Cdk1 activation is initiated by a trigger that reverses the balance of activities between Cdc25 and Wee1/Myt1 and is further accelerated by autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to be the cyclin A–Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce cyclin B–Cdk1 activation, cyclin A–Cdk1 is nonessential and hence the trigger remains elusive. Here, we show that SGK directly phosphorylates Cdc25 and Myt1 to trigger cyclin B–Cdk1 activation in starfish oocytes. Upon hormonal stimulation of the meiotic G2/M transition, SGK is activated by cooperation between the Gβγ-PI3K pathway and an unidentified pathway downstream of Gβγ, called the atypical Gβγ pathway. These findings identify the trigger in oocyte meiosis and provide insights into the role and activation of SGK.

The transition from meiosis to mitosis, classically defined by fertilization, is a fundamental process in development. However, its mechanism remains largely unexplored. In this paper, we report a surprising gradual transition from meiosis to mitosis over the first eight divisions of the mouse embryo. The first cleavages still largely share the mechanism of spindle formation with meiosis, during which the spindle is self-assembled from randomly distributed microtubule-organizing centers (MTOCs) without centrioles, because of the concerted activity of dynein and kinesin-5. During preimplantation development, the number of cellular MTOCs progressively decreased, the spindle pole gradually became more focused, and spindle length progressively scaled down with cell size. The typical mitotic spindle with centrin-, odf2-, kinesin-12–, and CP110-positive centrosomes was established only in the blastocyst. Overall, the transition from meiosis to mitosis progresses gradually throughout the preimplantation stage in the mouse embryo, thus providing a unique system to study the mechanism of centrosome biogenesis in vivo.

Meiosis, at the transition between diploid and haploid life cycle phases, is accompanied by reprograming of cell division machinery and followed by a transition back to mitosis. We show that, in Arabidopsis , this transition is driven by inhibition of translation, achieved by a mechanism that involves processing bodies (P-bodies). During the second meiotic division, the meiosis-specific protein THREE-DIVISION MUTANT 1 (TDM1) is incorporated into P-bodies through interaction with SUPPRESSOR WITH MORPHOGENETIC EFFECTS ON GENITALIA 7 (SMG7). TDM1 attracts eIF4F, the main translation initiation complex, temporarily sequestering it in P-bodies and inhibiting translation. The failure of tdm1 mutants to terminate meiosis can be overcome by chemical inhibition of translation. We propose that TDM1-containing P-bodies down-regulate expression of meiotic transcripts to facilitate transition of cell fates to postmeiotic gametophyte differentiation.

Katanin is an evolutionarily conserved microtubule (MT)-severing complex implicated in multiple aspects of MT dynamics. In Caenorhabditis elegans, the katanin homologue MEI-1 is required for meiosis, but must be inactivated before mitosis. Here we show that PPFR-1, a regulatory subunit of a trimeric protein phosphatase 4 complex, enhanced katanin MT-severing activity during C. elegans meiosis. Loss of ppfr-1, similarly to the inactivation of MT severing, caused a specific defect in meiosis II spindle disassembly. We show that a fraction of PPFR-1 was degraded after meiosis, contributing to katanin inactivation. PPFR-1 interacted with MEL-26, the substrate recognition subunit of the CUL-3 RING E3 ligase (CRL3MEL-26), which also targeted MEI-1 for post-meiotic degradation. Reversible protein phosphorylation of MEI-1 may ensure temporal activation of the katanin complex during meiosis, whereas CRL3MEL-26-mediated degradation of both MEI-1 and its activator PPFR-1 ensure efficient katanin inactivation in the transition to mitosis.

Meiosis is required to reduce to haploid the diploid genome content of a cell, generating gametes—oocytes and sperm—with the correct number of chromosomes. To achieve this goal, two specialized cell divisions without intermediate S-phase are executed in a time-controlled manner. In mammalian female meiosis, these divisions are error-prone. Human oocytes have an exceptionally high error rate that further increases with age, with significant consequences for human fertility. To understand why errors in chromosome segregation occur at such high rates in oocytes, it is essential to understand the molecular players at work controlling these divisions. In this review, we look at the interplay of kinase and phosphatase activities at the transition from metaphase-to-anaphase for correct segregation of chromosomes. We focus on the activity of PP2A-B56, a key phosphatase for anaphase onset in both mitosis and meiosis. We start by introducing multiple roles PP2A-B56 occupies for progression through mitosis, before laying out whether or not the same principles may apply to the first meiotic division in oocytes, and describing the known meiosis-specific roles of PP2A-B56 and discrepancies with mitotic cell cycle regulation.

Background Gametes are generated through a specialized cell division called meiosis, in which ploidy is reduced by half because two consecutive rounds of chromosome segregation, meiosis I and meiosis II, occur without intervening DNA replication. This contrasts with the mitotic cell cycle where DNA replication and chromosome segregation alternate to maintain the same ploidy. At the end of mitosis, CDKs are inactivated. This low CDK state in late mitosis/G1 allows for critical preparatory events for DNA replication and centrosome/spindle pole body (SPB) duplication. However, their execution is inhibited until S phase, where further preparatory events are also prevented. This “licensing” ensures that both the chromosomes and the centrosomes/SPBs replicate exactly once per cell cycle, thereby maintaining constant ploidy. Crucially, between meiosis I and meiosis II, centrosomes/SPBs must be re-licensed, but DNA re-replication must be avoided. In budding yeast, the Cdc14 protein phosphatase triggers CDK down regulation to promote exit from mitosis. Cdc14 also regulates the meiosis I to meiosis II transition, though its mode of action has remained unclear. Methods Fluorescence and electron microscopy was combined with proteomics to probe SPB duplication in cells with inactive or hyperactive Cdc14. Results We demonstrate that Cdc14 ensures two successive nuclear divisions by re-licensing SPBs at the meiosis I to meiosis II transition. We show that Cdc14 is asymmetrically enriched on a single SPB during anaphase I and provide evidence that this enrichment promotes SPB re-duplication. Cells with impaired Cdc14 activity fail to promote extension of the SPB half-bridge, the initial step in morphogenesis of a new SPB. Conversely, cells with hyper-active Cdc14 duplicate SPBs, but fail to induce their separation. Conclusion Our findings implicate reversal of key CDK-dependent phosphorylations in the differential licensing of cyclical events at the meiosis I to meiosis I transition.

Background: Gametes are generated through a specialized cell division called meiosis, in which ploidy is reduced by half because two consecutive rounds of chromosome segregation, meiosis I and meiosis II, occur without intervening DNA replication. This contrasts with the mitotic cell cycle where DNA replication and chromosome segregation alternate to maintain the same ploidy. At the end of mitosis, cyclin-dependent kinases (CDKs) are inactivated. This low CDK state in late mitosis/G1 allows for critical preparatory events for DNA replication and centrosome/spindle pole body (SPB) duplication. However, their execution is inhibited until S phase, where further preparatory events are also prevented. This “licensing” ensures that both the chromosomes and the centrosomes/SPBs replicate exactly once per cell cycle, thereby maintaining constant ploidy. Crucially, between meiosis I and meiosis II, centrosomes/SPBs must be re-licensed, but DNA re-replication must be avoided. In budding yeast, the Cdc14 protein phosphatase triggers CDK down regulation to promote exit from mitosis. Cdc14 also regulates the meiosis I to meiosis II transition, though its mode of action has remained unclear. Methods: Fluorescence and electron microscopy was combined with proteomics to probe SPB duplication in cells with inactive or hyperactive Cdc14. Results: We demonstrate that Cdc14 ensures two successive nuclear divisions by re-licensing SPBs at the meiosis I to meiosis II transition. We show that Cdc14 is asymmetrically enriched on a single SPB during anaphase I and provide evidence that this enrichment promotes SPB re-duplication. Cells with impaired Cdc14 activity fail to promote extension of the SPB half-bridge, the initial step in morphogenesis of a new SPB. Conversely, cells with hyper-active Cdc14 duplicate SPBs, but fail to induce their separation. Conclusion: Our findings implicate reversal of key CDK-dependent phosphorylations in the differential licensing of cyclical events at the meiosis I to meiosis II transition.

Disturbances of checkpoints in distinct stages of spermatogenesis (mitosis, meiosis, and spermiogenesis) contribute to impaired spermatogenesis; however, the efficiency of meiotic entry has not been investigated in more detail. In this study, we analyzed azoospermic patients with defined spermatogenic defects by the use of octamer-binding protein 2 for type A spermatogonia, sarcoma antigen 1 for mitosis–meiosis transition and SMAD3 for pachytene spermatocytes. Especially patients with maturation arrest (MA) at the level of primary spermatocytes showed significantly reduced numbers of spermatogonia compared with patients with histologically intact spermatogenesis or patients with hypospermatogenesis (Hyp). For a detailed individual classification of the patients, we distinguished between ‘high efficiency of meiotic entry’ (high numbers of pachytene spermatocytes) and ‘low efficiency of meiotic entry’ (low numbers of pachytene spermatocytes). Only patients with histologically normal spermatogenesis (Nsp) and patients with Hyp showed normal numbers of spermatogonia and a high efficiency of meiotic entry. Of note, only patients with histologically Nsp or patients with Hyp could compensate low numbers of spermatogonia with a high efficiency of meiotic entry. In contrast, patients with MA always showed a low efficiency of meiotic entry. This is the first report on patients with impaired spermatogenesis, showing that half of the patients with Hyp but all patients with MA cannot compensate reduced numbers in spermatogonia with a highly efficient meiosis. Thus, we suggest that compensatory meiosis mechanisms in human spermatogenesis exist.

Aperçu du contrôle de la dégradation des ARNm par les protéines YTHpendant la transition de la méiose à la mitose chez les levures.Le cycle cellulaire est contrôlé par des processus complexes et interconnectés. Un gène est transcrit en ARNm qui est traduit en protéines mais de nombreux processus de régulation travaillent pour contrôler chaque étape de ce processus apparemment simple. Parmi ces points de contrôle, la régulation post-transcriptionnelle est importante, et la formation d'un complexe protéine-ARN peut diriger le destin cellulaire. Parmi ces protéines de liaison à l'ARN, les protéines contenant des domaines YTH n’ont été découvertes qu’à la fin des années 90. Les protéines contenant des domaines YTH sont abondantes chez les eucaryotes et absentes chez les procaryotes. Elles constituent la majorité des protéines « readers » capables de reconnaître spécifiquement la modification m6A. L’Homme possède cinq protéines YTH, YTHDF1-3, YTHDC1,2 (Hazra, D., C. Chapat, et Graille, M. (2019). Destin de l'ARNm de m6A : enchaînés au rythme par les protéines contenant de la YTH. , 10 (1), 49.). Bien qu'il soit évident que ces protéines contrôlent le destin cellulaire, la fonction de chaque protéine et son réseau d’interaction restent à élucider. Chez les levures, une seule protéine YTH est présente: Pho92 chez Saccharomyces cerevisiae et Mmi1 chez Schizosaccharomyces pombe. Hormis le domaine YTH, il n'y a pas d'homologie de séquence entre ces deux protéines mais leur fonction cellulaire est similaire.Il est bien établi que Mmi1 est responsable de la dégradation des transcrits spécifiques de la méiose au cours de la croissance végétative des cellules chez la levure S. pombe. Mmi1 forme un complexe stable avec une petite protéine, Erh1 (complexe Erh1-Mmi1 ou EMC). Le complexe EMC peut physiquement interagir avec la sous-unité Not1 du complexe CCR4-Not et la recruter pour la dégradation des ARNm contenant des motifs DSR (déterminant de l'élimination sélective). L'action de Mmi1 est à son tour régulée par une protéine possédant un domaine RRM, Mei2. Au cours de la méiose, Mei2, avec l’aide d’un lncRNA meiRNA, séquestre Mmi1 dans un point nucléaire, le rendant inactif et assurant la continuité de la méiose. Ces trois protéines, Mmi1-Erh1-Mei2, jouent un rôle clé dans la transition de la mitose vers la méiose.Chez S. cerevisiae, Pho92 est impliquée dans la dégradation des transcrits de PHO4, contribuant à la voie du métabolisme du phosphate, pendant la privation en phosphate et participe également à la dégradation des ARNm contenant les marques épitranscriptomiques de N6-méthyladénosine (m6A). Comme pour S. pombe Mmi1, Pho92 recrute le complexe CCR4-Not via une interaction physique avec Not1.Au cours de ma thèse, j'ai tenté d'élucider le rôle de ces deux protéines du domaine YTH de deux organismes modèles, S. cerevisiae et S. pombe, dans la dégradation de l'ARNm et la régulation du cycle cellulaire par des approches biochimiques et structurales.Pho92 de S. cerevisiae interagit physiquement avec Not1 du complexe CCR4-Not, nous avons pu déterminer les limites des domaines impliqués dans cette interaction. L’interaction entre ces deux protéines a été étudiée par anisotropie de fluorescence. Le complexe protéique a été purifié avec succès et des essais de cristallisation sont en cours.Chez S. pombe, la structure de Mei2-RRM3 a été résolue avec et sans ARN. Les propriétés de liaison à l'ARN de Mei2-RRM3 ont été étudiées par ITC. La structure de Erh1 a également été résolue révélant une organisation en homodimere. Nous avons montré que la formation de cet homodimere est important pour la fonction biologique de Mmi1. Des essais de co-cristallisation ont été réalisés avec de l'ARN et les protéines Mmi1 et Mei2, mais sans succès et nous avons obtenu des cristaux de Mmi1
Insights into the control of mRNA decay by YTH proteinsduring the transition from meiosis to mitosis in yeasts.Keywords: Epitranscriptomics, mRNA decay, meiosis, multi-protein complexes, YTH domainCell cycle is controlled by multi-layered processes. A gene is transcribed in mRNA which is translated in proteins but innumerable regulation processes are working to control every step of this apparently simple process. Among these regulatory check points, post-transcriptional regulation is an important one, where formation of a protein-RNA complex may direct the cellular fate. Among these RNA binding proteins, YTH domain proteins are most novel, discovered in late 90s. YTH domain proteins are abundant in eukaryotes and absent in prokaryotes. YTH domain proteins constitute the majority of reader proteins that can specifically identify m6A modification. Human beings have five YTH domain proteins YTHDF1-3, YTHDC1-2 (Hazra, D., Chapat, C., & Graille, M. (2019). m6A mRNA Destiny: Chained to the rhYTHm by the YTH-Containing Proteins. Genes, 10(1), 49.). Although it is evident that these proteins are controlling cellular fate, the function of each protein and their network is yet to be elucidated. In yeast, there is only one YTH domain protein present: Pho92 in Saccharomyces cerevisiae and Mmi1 in Schizosaccharomyces pombe. Apart from the YTH domain there is no sequence homology between these two proteins but their cellular function is similar.It is well established that Mmi1 is responsible for degradation of meiosis specific transcripts during vegetative growth of the cell. Mmi1 forms a tight complex with a small protein, Erh1 (Erh1-Mmi1 complex or EMC). EMC can physically interact with Not1 of CCR4-Not complex and recruit it for degradation of DSR (determinant of selective removal) containing RNAs. The action of Mmi1 is in turn regulated by an RRM domain protein, Mei2. During meiosis, Mei2, along with a lncRNA meiRNA sequesters Mmi1 in a nuclear dot, rendering it inactive and ensuring smooth continuance of meiosis. These three proteins, Mmi1-Erh1-Mei2 play a key role in mitosis to meiosis switch.In S. cerevisiae, Pho92 is involved in the degradation of PHO4 transcripts contributing to phosphate metabolism pathway, during phosphate starvation and also participates in the degradation of mRNAs containing the N6-methyladenosine (m6A) epitranscriptomics marks. Similarly, to S. pombe Mmi1, Pho92 recruits CCR4-Not complex by physical interaction with Not1.During my PhD, I have tried to elucidate the role of these two YTH domain proteins from two model organisms, S. cerevisiae and S. pombe, in mRNA degradation and cell cycle regulation using biochemical and structural approaches.Pho92 of S. cerevisiae physically interacts with Not1 of CCR4-Not complex, we were able to determine the boundaries of this interaction. The interaction between these two proteins was studied by Fluorescence anisotropy. The protein complex was successfully purified and crystallization trials are ongoing.From S. pombe, structure of Mei2-RRM3 was solved with and without an RNA. RNA binding properties of Mei2-RRM3 was studied by ITC. The structure of Erh1 was also solved and we tried to elucidate its importance for biological function of Mmi1. A co-crystallization trial was performed with Mmi1-Mei2-RNA but it was unsuccessful and we ended up with Mmi1 crystals

La différenciation sexuelle est un mécanisme complexe, où une gonade indifférenciée, va se développer en testicule chez les mâles ou en ovaire chez les femelles. Le sexe chromosomique est à l'origine de la détermination sexuelle, en activant des voies de signalisation sexe-spécifique. Découvert en 1990, le gène SRY, présent sur le chromosome Y des mâles, est un gène qui a longtemps été décrit comme le régisseur de toute la différenciation sexuelle. En sa présence, les embryons XY se différencient en mâles, mais son absence est suffisante pour induire la différenciation femelle, « par défaut ». Or, la détermination du sexe est bien plus complexe, impliquant l'expression de nombreux gènes, dont les niveaux d'expression équilibrés activent la voie ovarienne et répriment simultanément la voie testiculaire ou vice versa. Le développement d'un ovaire ou d'un testicule repose sur la présence des cellules somatiques ainsi que des cellules germinales, les seules cellules capables de réaliser la méiose.La méiose, découvert en 1883, est également un événement dépendant de la détermination du sexe, étant donné qu'elle se produit pendant le développement embryonnaire chez la femelle, et en post-natal chez les mâles. Encore une fois, de nombreux gènes doivent être finement régulés pour l'initiation et le déroulement correct de la méiose. En effet, les cellules germinales prolifèrent activement, puis doivent perdre leur pluripotence et entrer en méiose chez les femelles, tandis qu'elles restent pluripotentes et rentrent en quiescence chez les mâles. Cette transition s'opère par un changement de programme génétique, qui n'est pas encore totalement compris.L'étude des différents acteurs régulant la différenciation sexuelle, autant au niveau somatique que germinale, est alors une priorité de mon équipe, spécialiste du développement gonadique embryonnaire.La méthylation en position 6 de l'adénine des molécules d'adénosine de l'ARN (m6A) est un mécanisme émergent et encore peu compris de la régulation de l'expression des gènes. Pourtant elle est la modification de l'ARN la plus courante et la plus conservée chez les eucaryotes, et son importance est soulignée par différentes pathologies résultant des dysfonctionnements de cette méthylation. A l'heure actuelle, elle est connue pour réguler des processus très variés comme des processus de métaboliques, de développement, de différenciation cellulaire ou de réponse au stress.C'est alors que nous avons décidé d'étudier le rôle de Wtap, un acteur du complexe de méthylation m6A, dans la détermination du sexe et la méiose. Mes recherches ont permis de comprendre dans un premier temps que Wtap est bien exprimé dans les différents types cellulaire de la gonade, et ce, pendant la fenêtre critique de la différenciation sexuelle. Dans un second temps, grâce à un modèle murin perte de fonction pour Wtap spécifiquement dans les cellules somatiques, nous avons pu montrer que ce gène est crucial pour la différenciation des cellules somatiques mâles et femelles. En effet, les cellules de Sertoli et de la granulosa semblent pour la majeure partie, bloquées dans un stade pré-cellules de soutient. Enfin, dans un dernier temps, cette fois ci avec un modèle murin permettant l'inactivation de Wtap dans les cellules germinales uniquement, nous avons également analysé une diminution de leur différenciation. Les cellules germinales ne sont plus totalement en capacité d'induire la méiose chez les femelles, et de rentrer en quiescence chez les mâles.Ces résultats indiquent que Wtap, est un acteur clé pour la régulation de la différenciation des cellules somatiques et germinales, autant chez le mâle que chez la femelle
Sexual differentiation is a complex mechanism where an undifferentiated gonad develops into a testis in males or an ovary in females. Chromosomal sex is at the origin of sexual determination, by activating sex-specific signaling pathways. Discovered in 1990, the Sry gene, found on the Y chromosome of males, has long been described as the regulator of all sexual differentiation. In its presence, XY embryos differentiate into males, but its absence is sufficient to induce female differentiation, “by default”. However, sex determination is far more complex, involving the expression of numerous genes, whose balanced expression levels activate the ovarian pathway and simultaneously repress the testicular pathway, or vice versa. The development of an ovary or testis relies on the presence of somatic cells as well as germ cells, the only cells capable of meiosis.Meiosis, discovered in 1883, is also a sex-determining event, as it occurs during embryonic development in females, and post-natal in males. Once again, many genes must be finely regulated for meiosis for correct initiation and progressing. Germ cells proliferate actively, then lose their pluripotency and enter meiosis in females, while they remain pluripotent and enter quiescence in males. This transition takes place by a change in the genetic program, which is not yet fully understood.The study of the various actors regulating sexual differentiation, at both somatic and germline levels, is therefore a priority for my team, which specializes in embryonic gonadal development.N6-methyladenosine (m6A) is an emerging and still poorly understood mechanism of gene expression regulation. Yet it is the most common and most conserved RNA modification in eukaryotes, and its importance is underlined by various pathologies resulting from dysfunctions of this methylation. It is currently known to regulate a wide variety of processes, including metabolism, development, cell differentiation and stress response.We therefore decided to investigate the role of Wtap, an actor in the m6A methylation complex, in sex determination and meiosis. Firstly, my research showed that Wtap is well expressed in different gonadal cell types during the critical window of sexual differentiation. Secondly, using a loss-of-function mouse model for Wtap specifically in somatic cells, we were able to show that this gene is crucial for the differentiation of male and female somatic cells. Indeed, most Sertoli and granulosa cells appear to be blocked in a pre-supporting state. Finally, using a mouse model in which Wtap is inactivated in germ cells only, we also analyzed a decrease in germ cell differentiation. Germ cells are no longer fully able to induce meiosis in females, and enter quiescence in males.These results indicate that Wtap is a key player in the regulation of somatic and germ cell differentiation in both males and females

The early history of life on Earth likely included a stage in which life existed as self-replicating protocells with single-stranded RNA (ssRNA) genomes. In this RNA world, genome damage from a variety of sources (spontaneous hydrolysis, UV, etc.) would have been a problem for survival. Selection pressure for dealing with genome damage would have led to adaptive strategies for mitigating the damage. In today’s world, RNA viruses with ssRNA genomes are common, and these viruses similarly need to cope with genome damage. Thus ssRNA viruses can serve as models for understanding the early evolution of genome repair. As the ssRNA protocells in the early RNA world evolved, the RNA genome likely gave rise, through a series of evolutionary stages, to the double-stranded DNA (dsDNA) genome. In ssRNA to dsDNA evolution, genome repair processes also likely evolved to accommodate this transition. Some of the basic features of ssRNA genome repair appear to have been retained in descendants with dsDNA genomes. In particular, a type of strand-switching recombination occurs when ssRNA replication is blocked by a damage in the template strand. Elements of this process appear to have a central role in recombinational repair processes during meiosis and mitosis of descendant dsDNA organisms.