Conserved cysteine-switches for redox sensing operate in the cyclin-dependent kinase inhibitor p21(CIP/KIP) protein family.

The cell cycle is a tightly regulated, dynamic process controlled by multiple checkpoints. When the prevention of cell cycle progression is needed, key effectors such as members of the p21 (CIP/KIP) inhibit cyclin-dependent kinases (CDKs). It is accepted that p21 does not sense DNA damage and that stress signals affect p21 indirectly.

Tolerating DNA damage by repriming: Gap filling in the spotlight.

Timely and accurate DNA replication is critical for safeguarding genome integrity and ensuring cell viability. Yet, this process is challenged by DNA damage blocking the progression of the replication machinery. To counteract replication fork stalling, evolutionary conserved DNA damage tolerance (DDT) mechanisms promote DNA damage bypass and fork movement.

A mitotic stopwatch determines cell fate.

Surveillance of mitotic timing prevents amplification of damaged cells.

The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage.

It is well-established that, through canonical functions in transcription and DNA repair, the tumor suppressor p53 plays a central role in safeguarding cells from the consequences of DNA damage. Recent data retrieved in tumor and stem cells demonstrated that p53 also carries out non-canonical functions when interacting with the translesion synthesis (TLS) polymerase iota (POLι) at DNA replication forks. This protein complex triggers a DNA damage tolerance (DDT) mechanism controlling the DNA replication rate.

Correction: Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.

[This corrects the article DOI: 10.1371/journal.pgen.