Publications by authors named "D A Chenoweth"
Many cancers use an alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT telomeric DNA synthesis occurs in ALT-associated PML bodies (APBs). However, the mechanisms by which APBs form are not well understood.
View Article and Find Full Text PDFThe mitotic checkpoint protein MAD1 is significantly overexpressed in several cancers, weakening the checkpoint and promoting mitotic slippage. Overexpressed MAD1 forms ectopic foci in mitotic cells, yet the biophysical nature of these foci and their contributions to mitotic slippage remain unclear. Here, we report that MAD1 foci are phase-separated condensates that shorten the mitotic duration by sequestering checkpoint proteins.
View Article and Find Full Text PDFMolecular processes are profoundly influenced by the biophysical properties of the cell interior. However, the mechanisms that control these physical properties, and the processes they impact remain poorly understood, especially in the nucleus. We hypothesized that some viruses might change the biophysical properties of the nucleus to favor virus survival and replication and found that herpes simplex virus 1 (HSV-1) increases the mesoscale fluidity of the nucleus.
View Article and Find Full Text PDFArticle Synopsis
- Phase separation creates membraneless compartments in the nucleus, such as heterochromatin domains and repair foci, influencing genetic stability.
- In Drosophila, safe homologous recombination for repeated DNA sequences requires their movement to the nuclear edge, with the process involving specific nucleoporins like Nup98 and interactions with proteins such as HP1.
- Nup98 forms distinct condensates that help mobilize these repair sites while preventing Rad51 from interfering, and disruptions in this pathway can lead to significant issues with chromosome repair and integrity.