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Lee, Ja Yil
School of Life Sciences
Research Interests
  • Investigated eukaryotic homologous recombination.

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Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B

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Title
Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B
Author
Cheon, Na YoungKim, Hyun-SukYeo, Jung-EunScharer, Orlando D.Lee, Ja Yil
Issue Date
2019-08
Publisher
Oxford University Press
Citation
NUCLEIC ACIDS RESEARCH
Abstract
DNA repair is critical for maintaining genomic integrity. Finding DNA lesions initiates the entire repair process. In human nucleotide excision repair (NER), XPC-RAD23B recognizes DNA lesions and recruits downstream factors. Although previous studies revealed the molecular features of damage identification by the yeast orthologs Rad4-Rad23, the dynamic mechanisms by which human XPC-RAD23B recognizes DNA defects have remained elusive. Here, we directly visualized the motion of XPC-RAD23B on undamaged and lesion-containing DNA using high-throughput single-molecule imaging. We observed three types of one-dimensional motion of XPC-RAD23B along DNA: diffusive, immobile and constrained. We found that consecutive AT-tracks led to increase in proteins with constrained motion. The diffusion coefficient dramatically increased according to ionic strength, suggesting that XPC-RAD23B diffuses along DNA via hopping, allowing XPC-RAD23B to bypass protein obstacles during the search for DNA damage. We also examined how XPC-RAD23B identifies cyclobutane pyrimidine dimers (CPDs) during diffusion. XPC-RAD23B makes futile attempts to bind to CPDs, consistent with low CPD recognition efficiency. Moreover, XPC-RAD23B binds CPDs in biphasic states, stable for lesion recognition and transient for lesion interrogation. Taken together, our results provide new insight into how XPC-RAD23B searches for DNA lesions in billions of base pairs in human genome.
URI
https://scholarworks.unist.ac.kr/handle/201301/27336
URL
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz629/5542879
DOI
10.1093/nar/gkz629
ISSN
0305-1048
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SLS_Journal Papers
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