Ovarian cancer cells with high p16 protein are sensitive to CDK2 inhibitors.

DNA double strand breaks can be repaired by several pathways leading to different genetic outcomes. Here, the authors define the interplay between the DNA damage response factors 53BP1-RIF1 and core n...

STAR Protocols is an open access, peer-reviewed journal from Cell Press. We offer structured, transparent, accessible, and repeatable step-by-step experimental and computational protocols from all are...

DNA damage threatens genome stability, but its dynamics in living systems remain difficult to track. Here, the authors engineer MCPH1-based protein probes that specifically recognize γH2AX, enabling r...

Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...

Analysis of the longest-lived mammal, the bowhead whale, reveals an improved ability to repair DNA breaks, mediated by high levels of cold-inducible RNA-binding protein.  &nbs...

Abstract. Clinical trials show benefit of the combination of poly(ADP-ribose) polymerase inhibitors (PARPi) with androgen receptor (AR) pathway inhibitors

Mutations in the ATRX chromatin remodeller predispose to a developmental genetic disorder and cancer, but how it safeguards genome and telomere stability remains unresolved. Here, we uncover critical ...

Saur, Lesage et al. report that RNA:DNA hybrids arise at double-strand breaks in transcribed genes, independently of de novo recruitment of RNA polymerase II/III, as a result of DSB-induced transcriptional repression.

The cell cycle is governed by tightly regulated checkpoints and proteogenomic oscillations that ensure genomic fidelity during cell proliferation. Dysregulation of the cell cycle can drive oncogenic transformation, and this positions it as a pivotal target in precision oncology. Recent advances reveal how proteomic and post-translational dynamics orchestrate cell-cycle phase transitions that are aberrantly disrupted in cancers. Therapeutic targeting of the CDK4/6 represents a cornerstone of cancer therapy, but resistance mechanisms limit its clinical efficacy. Emerging strategies such as targeted protein degradation, synthetic lethality, and combination immunotherapies further expand the therapeutic window. These innovations, coupled with biomarker-driven precision medicine, exploit cell-cycle vulnerabilities and transform them into an active tool to combat human cancers more effectively. This review highlights emerging mechanistic insights underlying tumorigenesis driven by an aberrant cell cycle and proposes potential therapeutics aimed at cell-cycle machinery-relevant targets.