Related Experiment Video
Updated: Jun 21, 2026

Capturing Common Fragile Site Breaks by Native γH2A.X ChIP
Published on: January 24, 2025
The G(2) DNA damage checkpoint: could this ancient regulator be the Achilles heel of cancer?
Karen Kuntz1, Matthew J O'Connell
1Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY, USA.
Abstract:
The maintenance of genomic integrity is important in normal cell growth and organism development, as well as in the prevention of cancer. Cell cycle checkpoints allow the cell time to complete replication and repair DNA damage before it can pass to the next cell cycle stage. These checkpoints ensure faithful segregation of one undamaged copy of the genome to each daughter cell. In humans, a DNA damage-based checkpoint signal in G(1) is propagated through activation of the tumor suppressor p53, which is mutated in many cancers. Chk1, a serine/threonine kinase, controls checkpoint responses in G(2). Chk1 is activated by the concerted action of many upstream proteins and prevents a cell from entering mitosis with damaged or incompletely replicated DNA. This checkpoint is conserved from the fission yeast, Schizosaccharomyces pombe through to humans. However, unlike p53, G(2) checkpoint genes are rarely if ever mutated in cancer cells. This suggests that these genes are essential for tumor cell viability and may represent valid anti-cancer drug targets. This review will describe the current understanding of the G(2) checkpoint including how the human biology has been informed by studies in fission yeast. It will also discuss the present status and future of potential cancer therapies aimed at inactivating this signaling pathway in tumor cells.
Related Concept Videos
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
Negative Regulator Molecules
The Cell Cycle Control System
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
The Cell Cycle Control System
Positive Regulator Molecules

