Our research is focused on the molecular mechanisms of DNA repair and mutagenesis that is directly related to cancers and other human diseases. To deal with various genotoxic stresses, cells developed a fascinating DNA repair network that surveils DNA damage, transduces signals, and eventually repairs the damage through many different mechanisms. We are interested in three repair mechanisms that are coupled with DNA replication: interstrand cross-link (ICL) repair, mismatch repair (MMR), and translesion synthesis (TLS). Our goals are to provide novel insights and strategies of modulating replication-coupled repair for better human health.
Interstrand Cross-Link Repair. ICLs are among the most toxic DNA lesions, since they covalently tether both duplex DNA strands and prevent essential DNA metabolic functions such as replication and transcription. Deficient ICL repair underlies the chromosomal instability and the hypersensitivity to DNA cross-linking agents in the cancer-prone syndromes such as Fanconi anemia. Currently, our group is trying to characterize the biochemical functions of Fanconi anemia proteins in order to understand how they are involved in the ICL damage recognition, assembly of repair complexes, and repair of the damage. Our lab employs an established in vitro reconstitution system with purified components, flow cytometry, confocal microscopy, and other state-of-the-art tools. Mismatch Repair (MMR) and Translesion synthesis (TLS).
MMR corrects mismatches generated during DNA replication. Deficient MMR is the direct cause of a cancer syndrome call Lynch Syndrome or hereditary nonpolyposis colorectal cancer (HNPCC). We are interested in understanding mechanisms of MMR. TLS is a very important DNA damage tolerance mechanism. Many novel DNA polymerases that are specialized in bypassing replication-blocking DNA damage have been identified in the last decade. We are interested in understanding how the TLS polymerases are recruited and regulated at the damaged replication fork.