Chromosomes and reproduction - mitotic aneuploidies
4 important questions on Chromosomes and reproduction - mitotic aneuploidies
Which origin of aneuploidy of cells is most affected when maternal ages increases?
Challenges of the zygotic divisons (first mitotic divisons)
- large cytoplasm -> dilution of check point proteins -> weak checkpoints
- G1 and G2 checkpoints are also weak
- protamine-tot-histone exchange in paternal chromatin
- DNA replication in 2 separate pronuclei
- No homologous recombination for DNA repair because DNA replication in 2 separate pronuclei.
- spindle assembly and positioning
- chromosomes form 2 separate pronuclei
- from acentrosomal (oocyte) to centrosomal (zygote)
- from extremely asymmetric (oocyte) to symmetric (zygote) cell division
Mechanisms responsible for errors in early embryos:
- permissive checkpoints (G1, G2, and M checkpoints)
- DNA replication stress
- incomplete pronuclei migration
- asynchrony and un-clustering of parental genomes
- Mal-positioning of centrosomes
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The completion of DNA replication in a zygote is in G2. DNA replication stress is induces by
- de-novo non-gametic DNA lesions occur during S-phase and can persist until the onset of mitosis.
- DNA replication is extremely slow in zygotes
- through increasing high origin density (zygote is low origin density) and frequent fork stalling
- checkpoint is permissive to incomplete DNA replication during late G2 phase in early phases in complete DNA replication leads to arrest of the cel division.
- the DNA replication stress makes errors in gene-poor regions of genome.
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