Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase.

Recent findings suggest important roles for nuclear organization in gene expression. In contrast, little is known about how nuclear organization contributes to genome stability. Epistasis analysis (E-MAP) using DNA repair factors in yeast indicated a functional relationship between a nuclear pore subcomplex and Slx5/Slx8, a small ubiquitin-like modifier (SUMO)-dependent ubiquitin ligase, which we show physically interact.

The processing of double-strand breaks and binding of single-strand-binding proteins RPA and Rad51 modulate the formation of ATR-kinase foci in yeast.

Double-strand breaks (DSB) in yeast lead to the formation of repair foci and induce a checkpoint response that requires both the ATR-related kinase Mec1 and its target, Rad53. By combining high-resolution confocal microscopy and chromatin-immunoprecipitation assays, we analysed the genetic requirements for and the kinetics of Mec1 recruitment to an irreparable HO-endonuclease-induced DSB. Coincident with the formation of a 3' overhang, the Mec1-Ddc2 (Lcd1) complex is recruited into a single focus that colocalises with the DSB site and precipitates with single-strand DNA (ssDNA).

Nuclear pore association confers optimal expression levels for an inducible yeast gene.

The organization of the nucleus into subcompartments creates microenvironments that are thought to facilitate distinct nuclear functions. In budding yeast, regions of silent chromatin, such as those at telomeres and mating-type loci, cluster at the nuclear envelope creating zones that favour gene repression. Other reports indicate that gene transcription occurs at the nuclear periphery, apparently owing to association of the gene with nuclear pore complexes.

Heterochromatin protein 1: don't judge the book by its cover!

The name heterochromatin protein 1 (HP1) suggests that this small nuclear factor plays a role in forming heterochromatic domains. It was noticed years ago, however, that the distribution of HP1 on polytene chromosomes was not restricted to chromocenters or telomeres. HP1 was also found, reproducibly, along the euchromatic arms.

Subtelomeric factors antagonize telomere anchoring and Tel1-independent telomere length regulation.

Yeast telomeres are anchored at the nuclear envelope (NE) through redundant pathways that require the telomere-binding factors yKu and Sir4. Significant variation is observed in the efficiency with which different telomeres are anchored, however, suggesting that other forces influence this interaction. Here, we show that subtelomeric elements and the insulator factors that bind them antagonize the association of telomeres with the NE.