Research ArticleDNA Repair

K63-linked polyubiquitin chains bind to DNA to facilitate DNA damage repair

See allHide authors and affiliations

Science Signaling  05 Jun 2018:
Vol. 11, Issue 533, eaar8133
DOI: 10.1126/scisignal.aar8133

DNA-bound ubiquitin coordinates DNA repair

Ubiquitylation is a posttranslational modification that reversibly alters protein stability, activity, interactions, or trafficking. The ubiquitylation of histones and various other proteins facilitates the response to DNA damage. However, Liu et al. discovered that ubiquitin also binds directly to DNA. In solution and in live cells, chains of ubiquitin specifically linked through Lys63 residues (referred to as K63-linked polyubiquitin chains) preferentially bound to the free ends of double-stranded DNA through a three-amino acid motif in ubiquitin that the authors call a “DNA-interacting patch” (DIP). These chains appeared to bind the broken ends of DNA and recruit repair proteins. Ubiquitins with mutations in the DIP were found in several types of tumors and, when expressed in cultured cells, impaired the cellular response to DNA-damaging agents, suggesting that these mutations might be exploited for therapeutic benefit in some cancer patients.

View Full Text

Stay Connected to Science Signaling