The Department of Biochemistry's weekly BCH 252 seminar series is presented this week by:

Feng He, PhD Candidate, BCMB Graduate Program, UC Riverside 

Seminar Title: "Structural Insights into DNA Binding and Opening by the XPB-Bax1 Helicase-Nuclease Complex"

Abstract: Nucleotide excision repair (NER) removes various DNA lesions caused by UV light and chemical carcinogens. The DNA helicase XPB plays a key role in DNA opening and coordinating damage incision by nucleases during NER, but the underlying mechanisms remain unclear for decades. Here, we report crystal structures of XPB from Sulfurisphaera tokodaii (St) bound to the nuclease Bax1 and their complex with a forked DNA. Remarkably, StXPB and Bax1 together spirally encircle 10 base pairs of duplex DNA at the double-/single-stranded (ds–ss) junction. Furthermore, StXPB has its ThM motif intruding between the two DNA strands and gripping the 3'-overhang while Bax1 interacts with the 5'-overhang. This ternary complex likely reflects the state of repair bubble extension by the XPB and nuclease machine. Structural analyses suggest that ATP binding and hydrolysis by StXPB could lead to its translocation along dsDNA and DNA opening by the ThM motif, revealing an unconventional DNA unwinding mechanism. Interestingly, the DNA is kept away from the nuclease domain of Bax1, potentially preventing DNA incision by Bax1 during repair bubble extension. Our structural and biochemical results also have important implications for XPB-mediated DNA opening in eukaryotic NER.

Faculty Host: Ernest Martinez; ernest.martinez@ucr.edu