Upon closer inspection, we demonstrate that Ku depletion activates cryptic splice acceptor sites within antisense Alu elements, which are located immediately upstream of a stem loop that Shan Zha’s group recently demonstrated to be bound by Ku70/80. 5/n

Using a Halo-PROTAC ligand we can degrade Halo-Ku70 and Halo-Ku80 and cells rapidly die! At an early timepoint before a substantial amount of cell death occurs, we observed dramatic changes in RNA splicing. Strikingly, antisense Alu elements were significantly enriched in miss-spliced introns. 4/n

In rare good news these days Hängen-Dasz has brought back pralines and cream! Even better, it was on sale!

But what about the role of MDC1 in homologous recombination in interphase cells? Josh’s results demonstrate that modulating the affinity of the PST-repeats for chromatin reduces HR efficiency in a reporter assay. 7/n

Using a cell line with a single Lac operator array on chromosome 1, Josh demonstrated that locally enriching just the PST-repeat region fuses to the Lac inhibitor at this site was sufficient to trigger chromosome missegregation. 4/n

But why does MDC1 have to be globally removed from chromatin in mitosis? To address this question Josh expressed non-phosphorylatable variants of MDC1, which led to dramatic chromosome missegregation. Essentially, chromosomes were “glued” together. 3/n

Josh identified conserved TP sites in the PST-repeat region of MDC1 that are phosphorylated in mitosis to displace MDC1 from chromatin. 3/n

In previous work, Josh demonstrated that MDC1 is constitutively chromatin associated using single-molecule imaging. Interestingly, he observed rare cells in which MDC1 was highly mobile, which turned out to be in mitosis. 2/n

Here is a fun little teaser! What DNA repair factor does this to mitotic chromosomes? Pre-print should be up any time now! Exciting work by @heyzajr.bsky.social!

Plus 750 rushing yards.