Increasing asynapsis may attenuate the MSUC response by sequestering BRCA1 at unrepaired DSBs. (a and b) In Dnmt3l^−/− pachytene spermatocytes, increasing asynapsis is associated with increasingly focal BRCA1 staining. In the two spermatocytes shown, the Y chromosome has failed to synapse with the X chromosome. (c and d) Enlargements of the X (presumed) and Y chromosomes show that BRCA1 covers the axes of both chromosomes from the spermatocyte with only the X and Y asynapsed, but, in the spermatocyte with more extensive asynapsis, the BRCA1 has become more focal on the presumed X and is restricted on the Y chromosome to a single focus. (e) Quantitation of the axially located BRCA1 in pachytene spermatocytes shows that it does not increase with increasing asynapsis (fitted blue regression line). The projected increase in BRCA1 signal if it was in proportion to the amount of asynapsed axis is denoted by the red line. (f) The focal BRCA1 staining seen when asynapsis is extensive is largely DSB associated, as indicated by costaining for RAD51. Bars, 10 μm.