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The chromatin environment at origins of replication is thought to influence DNA replication initiation in eukaryotic genomes. However, it remains unclear how and which chromatin features control the firing of early-efficient (EE) or late-inefficient (LI) origins. Here, we use site-specific recombination and single-locus chromatin isolation to purify EE and LI replication origins in Saccharomyces cerevisiae. Using mass spectrometry, we define the protein composition of native chromatin regions surrounding the EE and LI replication start sites. In addition to known origin interactors, we find the microtubule-binding Ask1/DASH complex as an origin-regulating factor. Strikingly, tethering of Ask1 to individual origin sites advances replication timing (RT) of the targeted chromosomal domain. Targeted degradation of Ask1 globally changes RT of a subset of origins, which can be reproduced by inhibiting microtubule dynamics. Thus, our findings mechanistically connect RT and chromosomal organization via Ask1/DASH with the microtubule cytoskeleton. [Display omitted] • Single-locus chromatin isolation shows distinct protein interactions at EE/LI origins • Ask1/DASH complex can regulate replication timing of ∼450 chromosomal locations • Ask1-activated regions are enriched for EE replication origins • Ask1-repressed regions are preferentially located at LI and inter-origin locations Weiβ et al. establish a system of native single-locus chromatin isolation in yeast to identify proteins associated with distinct early-efficient (EE) or late-inefficient (LI) replication origins. The results identify the microtubule-binding Ask1/DASH complex as an origin-regulating factor that connects chromosomal organization in the nucleus with replication timing control. [ABSTRACT FROM AUTHOR]

Voronoi diagrams were introduced by R. Klein as a unifying approach to Voronoi diagrams. In this paper we study furthest site abstract Voronoi diagrams and give a unified mathematical and algorithmic treatment for them. In particular, we show that furthest site abstract Voronoi diagrams are trees, have linear size, and that, given a set of n sites, the furthest site abstract Voronoi diagram can be computed by a randomized algorithm in expected time O(n log n). [ABSTRACT FROM AUTHOR]