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Comment
. 2020 Dec 15;117(50):31567-31569.
doi: 10.1073/pnas.2021185117. Epub 2020 Nov 16.

Hundreds of thousands of cell generations reveal a treasure chest of genome alterations

Juan Lucas Argueso  1 , Eric Alani  2
Affiliations
Comment

Hundreds of thousands of cell generations reveal a treasure chest of genome alterations

Juan Lucas Argueso et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1.
Fig. 1.
Formation of copy neutral loss of heterozygosity (CN-LOH) mutations and key Siu et al. (2) findings. (A) A pair of replicated homologous chromosomes in a model diploid cell. Blue and green indicate that the two homologs differ at discrete heterozygous sites (SNPs) distributed evenly across their entire lengths. The gap in the long arm of the left green chromatid represents a DNA double-strand break lesion to be repaired by homologous recombination (X). In this case, the template used in the repair reaction is the corresponding (allelic) DNA sequence present in the blue homolog, instead of the identical sequence from the green intact sister chromatid. This is a less frequent and less desirable template choice, but when it occurs either of the two possible recombination outcomes can lead to loss of SNPs present in the broken DNA molecule. In B, a gene conversion outcome of recombination involves a limited (kilobase scale) transfer of blue SNPs to the green chromatid, which following segregation leads to one of the two daughter cells carrying interstitial CN-LOH. In C, a crossing-over recombination outcome involves reciprocal exchange of all SNPs present between the break site and the telomere, potentially spanning megabase-long genomic regions. Additional sister chromatid segregation combinations that may restore heterozygosity are not shown for simplicity and to emphasize CN-LOH mechanisms.
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