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유전체 항상성 연구단
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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(s)
Na Young Cheon; Hyun-Suk Kim; Jung-Eun Yeo; Orlando D Schärer; Ja Yil Lee
Publication Date
2019-09
Journal
NUCLEIC ACIDS RESEARCH, v.47, no.16, pp.8337 - 8347
Publisher
OXFORD UNIV PRESS
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. C.The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
URI
https://pr.ibs.re.kr/handle/8788114/6272
ISSN
0305-1048
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
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