MRE11-RAD50-NBS1-CtIP: one key nuclease ensemble functions in the maintenance of genome stability

Abstract

To safeguard genome integrity, cells channel DNA double-strand breaks (DSBs) to repair pathway of either DNA end-joining or homology-directed repair. The MRE11-RAD50-NBS1 (MRN) complex functions in both pathways, teaming up with the right co-factors to ensure the correct repair of DSBs. The MRN complex is well known as a nuclease capable of resecting DNA in both endonucleolytic and exonucleolytic manners. At occupied DSB ends, DNA end resection is initiated by the “endonucleolytic cleavage followed by exonucleolytic digestion” action of MRN, with endonucleolytic cleavage specifically requiring phosphorylated CtIP being present. Previous studies by us and the other groups in the field help to uncover the mechanistic details of the MRN-CtIP nuclease ensemble functioning in DNA end resection and homologous recombination (HR), although many unclear parts still exist. Besides DSB repair, replication fork processing, R-loop, and transcription–replication conflict (TRC) resolution also have been suggested by accumulating studies to be relevant to MRN and CtIP. In this review, we will summarize current knowledge about the MRN-CtIP nuclease ensemble, its functions in DNA processing in various contexts that could generate genome instability, how this complex is regulated and its relevance to diseases like cancers.

Funding

National Natural Science Foundation of China(81972608)