Author ORCID Identifier

Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation

Genetics and Epigenetics

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Bin Wang

Committee Member

Lei Li

Committee Member

Junjie Chen

Committee Member

Boyi Gan

Committee Member

Katharina Schlacher

Committee Member

Xuetong Shen

Committee Member

John Tainer


DNA-protein crosslinks (DPCs) are a common DNA lesion naturally arising in cells, wherein protein becomes covalently and irreversibly bound to the DNA. Given their excessive size, these adducts present a significant challenge to replication and transcription, thus requiring timely and efficient repair. However, the precise mechanisms involved with processing DPC removal remain unclear. Moreover, current methodologies to quantitate DPC accumulation and removal are restrained by a range of limitations. Here, we describe and discuss a new DPC detection assay – the ARK assay – capable of overcoming the limitations incurred by prior assays. The design, which uses dual chaotropic lysis and anionic denaturation to remove excessive background signal, is premised upon isolating and measuring DPC-associated DNA and free, soluble DNA fragments. We show that the ARK assay effectively detects DPCs induced by a range of agents, and that DPC-defective models exhibit increased DPC accumulation. Functionally, we observe that Fanconi anemia pathway-inactivated cells incur increased DPC accumulation and delayed repair, suggesting a role for the Fanconi anemia pathway in the processing of these deleterious lesions.


DNA damage, DNA repair, DNA-protein crosslinks, Fanconi anemia, Nucleotide excision repair, SPRTN, ARK assay



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