ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway.

The ATR-CHK1 DNA damage response pathway becomes activated by the exposure of RPA-coated single-stranded DNA (ssDNA) that forms as an intermediate during DNA damage and repair, and as a part of the replication stress response. Here, we identify ZNF827 as a component of the ATR-CHK1 kinase pathway. We demonstrate that ZNF827 is a ssDNA binding protein that associates with RPA through concurrent binding to ssDNA intermediates. These interactions are dependent on two clusters of C2H2 zinc finger motifs within ZNF827. We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.

Learn locally, think globally. Exemplar variability supports higher-order generalization and word learning.

Research suggests that variability of exemplars supports successful object categorization; however, the scope of variability's support at the level of higher-order generalization remains unexplored. Using a longitudinal study, we examined the role of exemplar variability in first- and second-order generalization in the context of nominal-category learning at an early age. Sixteen 18-month-old children were taught 12 categories. Half of the children were taught with sets of highly similar exemplars; the other half were taught with sets of dissimilar, variable exemplars. Participants' learning and generalization of trained labels and their development of more general word-learning biases were tested. All children were found to have learned labels for trained exemplars, but children trained with variable exemplars generalized to novel exemplars of these categories, developed a discriminating word-learning bias generalizing labels of novel solid objects by shape and labels of nonsolid objects by material, and accelerated in vocabulary acquisition. These findings demonstrate that object variability leads to better abstraction of individual and global category organization, which increases learning outside the laboratory.