Viral manipulation of DNA repair and cell cycle checkpoints

Abstract

Recognition and repair of DNA damage is critical for maintaining genomic integrity and suppressing tumorigenesis. In eukaryotic cells, the sensing and repair of DNA damage are coordinated with cell cycle progression and checkpoints, in order to prevent the propagation of damaged DNA. The carefully maintained cellular response to DNA damage is challenged by viruses, which produce a large amount of exogenous DNA during infection. Viruses also express proteins that perturb cellular DNA repair and cell cycle pathways, promoting tumorigenesis in their quest for cellular domination. This review presents an overview of strategies employed by viruses to manipulate DNA damage responses and cell cycle checkpoints as they commandeer the cell to maximize their own viral replication. Studies of viruses have identified key cellular regulators and revealed insights into molecular mechanisms governing DNA repair, cell cycle checkpoints, and transformation.

Viral interactions with ATM/ATR checkpoint pathways and cell cycle regulators. Grey circles and arrows indicate cellular proteins and regulatory networks. Viral proteins boxed in green denote interactions that promote cell cycle progression. Effects of the viral proteins (shaded boxes) on their cellular substrates are indicated by the shaded triangles. Red triangles indicate interactions that are inhibitory to the targeted cellular factors, and green triangles denote interactions that promote activity of the targeted cellular factors. The interactions listed are limited to those covered in this review, and many more viral examples exist that have not been covered here.