Greehey CCRI Seminar Series – Fall ’25: Xiaoyu Xue, PhD (Texas State)
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My previous research focused on understanding conserved mechanisms of DNA replication and repair using biochemistry, genetics, cell biology, and structural biology methods. In particular, my studies have provided mechanistic information on how the FANCM/Mph1/Fml1 family DNA motor proteins, mutated in the cancer-prone disease Fanconi anemia, mediate DNA replication fork repair and the regulation of DNA break repair by homologous recombination. I demonstrated for the first time how the budding yeast FANCM ortholog Mph1 catalyzes replication fork regression and DNA recombination steps, and how its activities are differentially regulated in vitro and in cells by conserved SMC and histone fold complexes (Xue et al., Mol Cell 2014; Xue et al., Genes Dev 2015). I further discovered a new Mph1 partner, Mte1, and defined its roles in regulating Mph1 (Xue et al., Genes & Dev 2016). These studies provide a paradigm for understanding DNA helicase-mediated control of replication fork regression and recombination. These and other research findings are summarized in a review (Xue et al., Genes & Dev 2015).
Currently, research in the Xue group investigates how DNA/RNA motor proteins enable precise DNA repair to avoid cell transformation and tumorigenesis (Figure). We have obtained critical preliminary data on two human helicases and established a strong foundation for mechanistic studies in my laboratory. My research projects include: (1) Roles of nucleic acid motor protein ZGRF1 in chromosome damage repair and disease avoidance, (2) Functions of the DNA/RNA motor protein AQR in R-loop resolution. Both lines of studies have great potential for the development of novel strategies to treat human diseases that stem from defects or deregulation in DNA repair, such as Fanconi anemia, neurodegeneration diseases, and familial breast and ovarian cancers. Thus, my studies are both fundamentally important and clinically relevant.