Checkpoints articles from across Nature Portfolio

Errors in chromosome segregation during cell division lead to changes in nuclear features. A study now shows that a mechanosensitive nuclear checkpoint activates the tumour suppressor p53 to halt the proliferation of aneuploid cells. These findings provide mechanistic insights to explore in both ageing and cancer pathologies.

Telomere shortening causes replicative senescence but affects population growth in a complex manner. Here, the authors develop a mathematical model calibrated on yeast single-cell data which simulates cell populations undergoing senescence to gain insights into structural and dynamic properties.

Fulcher et al. show that MDM2 times mitosis through self-catalysed ubiquitination and proteasomal destruction, triggering G1 arrest following delays in mitosis associated with chromosome instability and aneuploidy.

Polo-like kinase 1 (PLK1) protects against genome instability by ensuring timely and accurate mitotic cell division. Here, the authors show that human PLK1 activity is sustained by the DNA damage response kinase Checkpoint kinase 2 (Chk2) in mitosis.

The role of PARylation, a modification with NAD⁺ as substrate, in Magnaporthe oryzae virulence is investigated. MoPARP1-mediated PARylation of 14-3-3 proteins is found to be required for activation of Pmk1, the key mitogen-activated kinase dictating appressorium development and virulence.

CDC25 phosphatases are attractive anticancer drug targets that regulate CDK activity. Here, the authors present the cryo-EM structure of the CDK2-cyclin A-CDC25A complex at 2.7 Å resolution, detailing key protein-protein interactions.

Errors in chromosome segregation during cell division lead to changes in nuclear features. A study now shows that a mechanosensitive nuclear checkpoint activates the tumour suppressor p53 to halt the proliferation of aneuploid cells. These findings provide mechanistic insights to explore in both ageing and cancer pathologies.

A cardinal rule of DNA replication is to prevent any possibility of pre-replication complexes re-loading during S phase, risking genotoxic over-replication. But can this rule be broken in emergency situations to preserve genome integrity?

The kinase ATR senses the completion of DNA replication and controls the S/G2 cell-cycle transition.

Immune checkpoint inhibitors are associated with durable and well-tolerated responses in metastatic urothelial carcinoma. Predicting which patients respond to therapy has been challenging; however, progress has been made using programmed cell death 1 ligand 1 as a biomarker and a second generation of biomarkers, which are being assessed.