| 總結: | <p>Our genome is continuously under various sources of genotoxic stresses. Thus, human has developed several DNA repair pathways to deal with different types of DNA damage. This thesis contains two studies, one focusing on the Fanconi Anemia pathway, which is known to coordinate the DNA interstrand crosslink repair, and the other one on the regulation of translesion synthesis, which is responsible for replication at DNA lesion sites, e.g. UV induced pyrimidine dimers.</p><p>Fanconi Anemia (FA) is a genetic disorder caused by mutations in any of 15 FA genes, where patients usually have developmental defects and predisposition to cancers in addition to anemia, and all the patients and patient derived cell lines are hypersensitive to DNA crosslinking agents such as Mitomycin C (MMC) and Cisplatin. Of the 15 FA proteins, FANCD2 and FANCI are key players essential for the functionality of the pathway. Upon genotoxic stress, both proteins are phosphorylated, ubiquitinated, and quickly recruited to sites of DNA damage together with other DNA repair proteins. In this part of our studies, we present the structure of the full-length human FANCD2/FANCI heterodimer, and our attempts at generating ubiquitinated FANCD2/FANCI heterodimer.</p><p>Polymerase η is one of the Y-family polymerases that are involved in translesion synthesis. It is known that ubiquitination and phosphorylation are together regulating the recruitment of polymerase η. In this part of our studies, we identified several novel polymerase η interacting proteins, as well as two novel phosphorylation sites, which could participate in the process of polymerase η recruitment upon DNA damage.</p>
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