CRL4 Ubiquitin Pathway and DNA Damage Response.

DNA damage occurs in a human cell at an average frequency of 10,000 incidences per day by means of external and internal culprits, damage that triggers sequential cellular responses and stalls the cell cycle while activating specific DNA repair pathways. Failure to remove DNA lesions would compromise genomic integrity, leading to human diseases such as cancer and premature aging. If DNA damage is extensive and cannot be repaired, cells undergo apoptosis. DNA damage response (DDR) often entails posttranslational modifications of key DNA repair and DNA damage checkpoint proteins, including phosphorylation and ubiquitination. Cullin-RING ligase 4 (CRL4) enzyme has been found to target multiple DDR proteins for ubiquitination. In this chapter, we will discuss key repair and checkpoint proteins that are subject to ubiquitin-dependent regulation by members of the CRL4 family during ultraviolet light (UV)-induced DNA damage.