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Aneuploidy in Human Oocytes and Preimplantation Embryos
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
MeioMapping also revealed some unexpected features of recombination and its effect on chromosome segregation. Normally, crossing over has been considered on a per bivalent basis such that if a crossover occurred between the two homologous chromosomes, chromosome segregation would proceed with high fidelity. This was referred to as the “obligate” crossover (e.g., [100]). However, Ottolini, et al. (2015) found that what happens to individual chromatids also influences their segregation. Non-recombinant chromatids that did not engage in recombination reactions (although its sister chromatid did) are vulnerable and at increased risk of undergoing PSSC/predivision (Figure 8.9). These findings open new areas of investigation as access to oocytes and new single-cell technologies improve.
Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The Aurora kinases, consisting of Aurora A, B, and C, are serine/threonine kinases that control numerous aspects of cell division in mammalian cells. They were first identified in 1990, although the meiotic and mitotic importance of Aurora A was not realized until 1998. The scattered mitotic spindles in cells generated by mutant forms of these enzymes resemble the Aurora Borealis (i.e. the “Northern Lights”) which gave rise to their name. Essentially, these enzymes help a dividing cell to distribute its genetic material to daughter cells by controlling chromatid segregation.
Introductory Remarks
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Structurally, each chromosome consists of two sister chromatids (or two identical chromosome copies) that are connected (aligned) in the centromeric region (or centromere), giving the appearance of an X (or H), and separating each chromatid (chromosome copy) into a short (p) arm and a long (q) arm, which together form about 400 total bands in a karyotype using Giemsa stain. At the ends of linear chromatids (chromosome copies) are telomeres (repetitive stretches of DNA) that lose a bit of the DNA with each cell division. A cell dies when all of the telomere DNA is lost [5]. However, some malignant cells manage to acquire the ability to keep their telomeres intact during division, and thus facilitate their continued/uncontrolled growth. Further, heterozygous germline mutation refers to change in a gene on one chromatid in germ cells (egg or sperm), which is inherited from a parent; homozygous germline mutations refer to similar changes in a gene on both chromatids in germ cells, which are inherited from two carrier parents; and compound heterozygous germline mutations refer to distinct changes in a gene involving both chromatids in germ cells, which are inherited from two carrier parents.
Cadmium exposure and DNA damage (genotoxicity): a systematic review and meta-analysis
Published in Critical Reviews in Toxicology, 2022
Raju Nagaraju, Ravibabu Kalahasthi, Rakesh Balachandar, Bhavani Shankara Bagepally
The frequency of SCE and chromosomal aberrations (CAs) in peripheral blood lymphocytes are extensively studied to screen genotoxicity in occupational settings (Roussel et al. 2019; Meyer et al. 2020). In this SRMA, three studies have used SCE to predict genotoxicity in the Cd-exposed group. SCE represents physical exchanges of the parental strands in the duplicated chromosomes during replication. Therefore, it is used as a genetic indicator for potential genotoxins/mutagens, as most forms of DNA damage induce chromatid exchange upon replication fork collapse (Wilson and Thompson 2007). SCE is a more sensitive biomarker for genotoxic effects than structural aberrations (Tucker and Preston 1996). In the present SRMA, the frequency of SCEs is elevated among the Cd-exposed than the unexposed group. The findings show the possibility of DNA damage among the Cd-exposed group.
Targeting the DNA damage response in pediatric malignancies
Published in Expert Review of Anticancer Therapy, 2022
Jenna M Gedminas, Theodore W Laetsch
Double stranded DNA breaks can be repaired using nonhomologous end joining repair (NHEJ) or homologous recombination (HR). The repair mechanism used is based on the stability of the end of the DNA breaks [11]. NHEJ directly ligates broken DNA without the need for a homologous template [12]. Because it does not rely on a template, it is able to repair double stranded breaks in any phase of the cell cycle, however, it is also more prone to error than homologous recombination. Homologous recombination is responsible for the reactivation of stalled replication forks and repair of double stranded DNA breaks and inter-strand crosslinks [13]. The repair process occurs in three steps. The broken end of the chromosome if first paired with the homologous region on the sister chromatid. That strand is then invaded to form a Holliday junction, or DNA crossover, which generates a DNA duplex from the two different chromatids [14]. The Holliday junction is then translocated along the DNA and eventually cleaved by endonucleases to again form separate DNA molecules [14]. These two processes are activated by several kinase pathways, ataxia telangiectasia mutated (ATM), ataxia telangiectasia related (ATR), and DNA-PK, which when mutated, result in defective double-strand break repair [15].
Chromosome aberration in typical biological systems under exposure to low- and high-intensity magnetic fields
Published in Electromagnetic Biology and Medicine, 2020
Emanuele Calabrò, Hit Kishore Goswami, Salvatore Magazù
It is known that the most crucial stage of mitotic division is the interphase wherein each very long chromatin thread (actually, chromatid) becomes a chromosome by way of replication of DNA and the immediate influence becomes operative of coiling and condensation so as to result in making compact chromosome. This packaging of DNA by tortuously folding and compacting into shaping a thick rod-shaped chromosome with two chromatids continues until early metaphase. It is precisely at this stage that alignment of chromosomes along the direction of the applied magnetic field was observed after exposure, such as it appears in Figures 7c–d and 9b. These changes have been the most common and repeated results observed in root tip preparations of both garlic and broad bean.