PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 4096695

The meiotic process and aneuploidy.

R F Grell
View original source ↗Export metadata ↓

Abstract

Normal females developing at 25 degrees C produce their first population of oocytes at 132 +/- 2 hr post oviposition. Entrance of the oocytes into premeiotic interphase signals initiation of DNA replication which continues for 30 hr. Coincidentally, extensive SCs appear, averaging 50 microns (132 hr), peaking at 75 microns (144 hr), and continuing into early vitellarial stages. Recombinational response to heat, evidenced by enhancement or induction of exchange, is limited to the S-phase with a peak at 144 hr coinciding with maximal extension of the SC. Coincidence of synapsis and recombination response with S at premeiotic interphase is contrary to their conventional localization at meiotic prophase. The interrelationship between exchange and nondisjunction has been clarified by the Distributive Pairing Model of meiosis. Originally revealed through high frequencies of nonrandom assortment of nonhomologous chromosomes, distributive pairing has been shown to follow and to be noncompetitive with exchange, to be based on size-recognition, not homology, and as a raison d'etre, to provide a segregational mechanism for noncrossover homologs. Rearrangements, recombination mutants, and aneuploids may contribute noncrossover chromosomes to the distributive pool and so promote the nonhomologous associations responsible for nondisjunction of homologs and regular segregation of nonhomologs. Further information concerning early meiotic events and their relation to segregation has been revealed by studies of the ts rec-1(26) mutant. Application of the restrictive temperature (31 degrees C) at sequential times during development shows wild-type activity to be drastically reduced beginning at 126/132 hr, terminating at 162 hr, and so coinciding with S and the heat-sensitive period of the normal genome. EMs of serially sectioned oocyte nuclei maintained at the restrictive or control temperature reveal SCs to be indistinguishable, and implicate recombination rather than synapsis as the target of the mutant. Activity of rec-1(26) in the range 17 degrees to 31 degrees C reveals a sharp decline between 28+ degrees and 31 degrees C, typical of a denaturation curve. If denaturation of the rec protein by the restrictive temperature marks its active phase, it follows that recombination terminates at the end of S when the restrictive temperature becomes ineffective. The notion that synapsis ensures regular segregation (35) is invalidated by rec-1(26) whose normal synapsis at the restrictive temperature is followed by a 200-fold increase in nondisjunction at segregation, as compared to the control.(ABSTRACT TRUNCATED AT 400 WORDS)

Explore related subjects

AneuploidyAnimalsDNA ReplicationDrosophilaFemaleInterphaseMeiosisMicroscopy, ElectronMutationOocytesOvaryOvipositionPupaJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

R F Grell. 1985. The meiotic process and aneuploidy.. https://doi.org/10.1007/978-1-4613-2127-9_22

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.

Advanced maternal age is a well-established risk factor for adverse reproductive outcomes due to increased rates of aneuploidy. However, emerging evidence indicates that the genetic consequences of maternal aging extend well beyond chromosome mis-segregation. Aging oocytes acquire a broad spectrum of genetic abnormalities, including maternally derived nuclear de novo mutations (DNMs) and mitochondrial DNA mutations, together with epigenetic dysregulation of DNA methylation and post-translational modification levels. These changes reflect the unique biology of the female germline in which oocytes remain arrested in meiotic prophase I for decades. Age-related deterioration of key processes, such as erosion of cohesion complexes, altered meiotic recombination, and weakened spindle assembly checkpoint surveillance collectively destabilize meiotic chromosome architecture, directly driving chromosome mis-segregation. At the same time, accumulation of endogenous DNA damage and declining DNA damage and repair processes increase the chances of transmitting lesions that can be converted into sequence-level mutations during the earliest embryonic divisions, when genome maintenance relies exclusively on maternal factors. High-resolution sequencing studies further demonstrate that maternal aging is associated with increased DNMs burden in both nuclear and mitochondrial DNA. Together, these findings support a model in which maternal aging is a driver of genome-wide instability that links aneuploidy and mutagenesis through shared defects in meiotic surveillance, declining DNA repair efficiency, and mitochondrial function. This framework positions delayed childbearing as a multifaceted genetic risk factor that extend beyond aneuploidy to include mutations and other genomic alterations that can impact intergenerational genetic risk.

Aneuploidy↗
PubMed2025

Modeling and targeting general and chromosome-specific aneuploidy in cancer.

Throughout the last century, aneuploidy has been cemented as a hallmark of cancer. Although the association of aneuploidy with tumorigenesis has been well established, the role of these genetic imbalances in tumor formation has only recently begun to be elucidated. Advancements in genomics have revealed the complexity and context dependence of the effect of aneuploidy on cancer growth, while developments in genetic editing have allowed for proper modeling of specific aneuploidies. In this review, we discuss the key factors to consider when studying the role of aneuploidy in cancer and the tools that are available to do so. We then highlight recent studies that establish phenotypic contributions of aneuploidy to tumorigenicity. In particular, we highlight how general aneuploidy and chromosomal instability affect the tumor microenvironment and how specific chromosomal alterations, including the loss of chromosome 9p and the gain of chromosomes 8q and 1q, influence tumor behavior and therapeutic responses. Finally, we emphasize the potential of targeting aneuploidy-induced vulnerabilities to improve cancer treatment outcomes.

Aneuploidy↗