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Chromosomal segregation and homology directed repair, how?


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Hi there,

I have been recently been thinking about the determinant chromosomal positions we see for each chromosome within a given cell type, many of the chromosome pairs are quite far away inside the nucleus, and these positions seem to not be moving that much at all (that is, we can consistently find the same/similar topology in a given cell type). Now that is all good and nice, but it breaks my expectation of homology directed repair (HDR) a bit. In HDR, a double-stranded break on one chromosome is fixed through the recruitment of the other chromosome, and while I am aware that HDR is not as frequently employed within a cell as NHEJ (non homologous end joining), text books and research will still show that HDR exists.
How can the segregated chromosomes still facilitate HDR, does the whole chromosome move or is only a specific region of chromosome xA moved to chromosome xB? If so, how does the cell know where to go, and how can in this time frame NHEJ not already have fixed it?

The only thing I can personally think of, is that HDR is only likely in proliferating cells, where the chromosomal topology changes during M phase? or during the S-phase and G1 as then each chromosome has a duplicate closeby (which would mean HDR has only a small window to work in)?

Kind regards,
Dagl

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