2023
DOI: 10.1101/2023.10.06.561239
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Chromosome Pairing Through Tensioned DNA Tethers Revealed by BRCA2 Meiotic Domain Deletion

Lieke Koornneef,
Sari E. van Rossum-Fikkert,
Esther Sleddens-Linkels
et al.

Abstract: BRCA2 has multiple functional domains that interact with different partners, and is essential for both somatic and meiotic homologous recombination (HR). We created aBrca2Δ12-14mouse model with an internal deletion of the region which we named “the meiotic domain of BRCA2”, as its loss results in complete failure of meiotic HR, while somatic HR is intact. The deletion in the protein includes the HSF2BP-binding motifs (exons 12-13) and the DMC1-binding PhePP domain (exon 14).Brca2Δ12-14mice showed complete infe… Show more

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Cited by 5 publications
(10 citation statements)
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“…In addition to BRCA2-S3291, the adjacent highly conserved BRCA2-F3298 is essential for the TR2-RAD51 interaction, and the surrounding conserved sequence matches the P-motif consensus ( 29 ). Thus, whereas our Brca2 Δ12–14 mouse model supports a meiotic function for the interaction between the BRCA2 P-motif encoded by exon 14 and DMC1, another BRCA2 P-motif encoded by exon 27 binds to RAD51, suggesting that interactions between P-motifs and recombinases may share structural and functional properties ( 20 ).…”
Section: Introductionmentioning
confidence: 76%
See 3 more Smart Citations
“…In addition to BRCA2-S3291, the adjacent highly conserved BRCA2-F3298 is essential for the TR2-RAD51 interaction, and the surrounding conserved sequence matches the P-motif consensus ( 29 ). Thus, whereas our Brca2 Δ12–14 mouse model supports a meiotic function for the interaction between the BRCA2 P-motif encoded by exon 14 and DMC1, another BRCA2 P-motif encoded by exon 27 binds to RAD51, suggesting that interactions between P-motifs and recombinases may share structural and functional properties ( 20 ).…”
Section: Introductionmentioning
confidence: 76%
“…whether BRCA2 coordinates both recombinases directly or affects DMC1 indirectly via its effect on RAD51 ( 13 , 19 ). We engineered a mouse with an internal deletion of Brca2 exons 12–14, the region we called ‘the meiotic domain of BRCA2’ because only meiotic functions were abolished ( 20 ). In the females, we found that DMC1 foci became undetectable, but RAD51 foci remained.…”
Section: Introductionmentioning
confidence: 99%
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“…In yeast, this is about 60-70% of the diameter of the nucleus (∼2.5-3 µm), and end-led motion involves appropriate displacements 12 . However, there are hints of long-range interactions of similar length in plants and mice 25,31,32 , and cytoskeleton-mediated motions involve similar mechanisms in all organisms and thus might be expected to be similar in magnitude in all cases. If the same RHJ onset requirement pertains generally across organisms, it would be a powerful mechanism for ensuring that homologs were already in a joint space before the dramatic events of juxtaposition are initiated.…”
Section: Discussionmentioning
confidence: 99%