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Phosphorylation of CENP-A on serine 7 has been proposed to control centromere assembly and function. Here, the authors use gene targeting at both endogenous CENP-A alleles and gene replacement in human cells to demonstrate that CENP-A that cannot be phosphorylated at serine 7 maintains correct CENP-C recruitment, faithful chromosome segregation and long-term cell viability.

Extensive DNA damage occurs during the first interphase following induction of tetraploidy in human cells, largely as a result of the lower amount of protein relative to DNA.

Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.

Centromeres are chromosomal domains epigenetically specified by the presence of the CENP-A containing nucleosomes that control chromosome segregation. Here the authors show that α-amino trimethylation of CENP-A by the enzyme NRMT is required for centromere function, faithful chromosome segregation and cell survival.

In mitosis, genome integrity is maintained by DNA polymerase theta-dependent repair of DNA double-strand breaks, which is regulated by Polo-like kinase 1 activity.

Chromosomal instability leads to aneuploidy, a state of karyotype imbalance. By inducing controlled chromosome mis-segregation, Santaguida and colleagues show that aneuploidy can also instigate chromosomal instability.

Centromeres play an essential function in faithful chromosome segregation. Here, the authors demonstrate the mechanism by which human cells dynamically modulate the activity of the Bloom’s syndrome helicase complex to safeguard centromere integrity throughout mitotic progression.

Centromere maintenance depends on the persistence of the histone variant CENP-A at the centromeres. Here, the authors characterize the core centromeric nucleosome complex wherein CENP-C confers a stable CENP-A nucleosome conformation and CENP-N fastens CENP-A to the DNA.

Topoisomerase 1 (Top1) inhibition is believed to mediate cellular toxicity by trapping Top1 on nicked DNA, leading to double-strand break formation during replication. New studies show that clinically relevant doses of Top1 poisons lead instead to extensive replication-fork reversal that is mediated by Poly(ADP-ribose) polymerases, limiting double-strand break formation.

The centromere-specific histone H3 variant CENP-A is sufficient for centromere specification in many species. Cleveland and colleagues have used an elegant gene targeting strategy to define a two-step mechanism for how CENP-A acts in centromere targeting and kinetochore assembly and function.

Centromeres are the chromosomal domains that regulate assembly of the components required for chromosome separation. Here the authors review how centromeres are a potential source of genome instability and link centromere aberrations and rearrangements to human diseases such as cancer.

Centromeres are a self-propagating chromatin structure that feature nucleosomes containing histone H3 variant CENP-A. Here, the authors screen for factors that play a role in CENP-A chromatin maintenance, finding that SUMO-protease SENP6 controls inheritance of chromatin bound CENP-A and is required for the maintenance of the centromere and kinetochore complex.

During the cell cycle, the centromeres of chromosomes have important roles and face key challenges, such as mediating successful chromosome segregation during mitosis and faithfully propagating their chromatin state to daughter chromosomes during S phase. This Review describes cell cycle-related features of centromeres, focusing on the nature and dynamics of centromeric chromatin, how it is intricately regulated and the potential implications for disease when these processes are disrupted.