Shan Yan

Shan Yan, PhD, Professor and Associate Chair for Research

Research Interests: Molecular Mechanisms of Genome Integrity

Research Areas: Cancer Biology, Cell Biology, Molecular Biology, Developmental Biology, Environmental Health, Xenopus laevis

All eukaryotes have evolved an elaborate network, DNA damage response (DDR), to detect aberrant DNA structures or stalled replication forks, and to coordinate DNA repair, checkpoint activation, cell cycle arrest, and senescence/apoptosis. From a broader perspective, the DDR machinery plays important roles in fundamental biomedical fields, such as DNA replication, DNA damage repair, cell cycle regulation, transcription, apoptosis, senescence, and autophagy. Defective DDR pathways compromise genomic integrity, leading to human diseases.

The research projects in the Yan lab focus on several essential questions linking DDR and human diseases, such as cancer, sepsis, aging, and neurodegenerative disorders. Using biochemical, molecular and cell biology approaches, our laboratory is interested in crucial issues in maintaining genomic stability, including checkpoint activation, DNA damage repair, and translesion synthesis (TLS) in response to DNA replication stress and oxidative stress as well as other stressful conditions. Ultimately, our research program will help to better understand how cells maintain genome stability and to provide novel clues for detection and treatment of human diseases. Xenopus egg extracts and mammalian cell lines will be used as model systems to investigate fundamental biomedical questions with cutting-edge technologies. One aim of this lab is to establish a motivated and productive research team. You are welcome to visit and/or join us!

Research Projects:

(1) DNA Single-strand break repair and signaling

(2) Oxidative stress response and redox regulation

(3) DNA replication stress response in genome stability

(4) DNA repair and DNA damage response pathways in human diseases (cancer, sepsis, aging, and neurodegenerative diseases)

Representative Publications (*corresponding author):

(10) Lin Y, Li J, Zhao H, McMahon A, McGhee K, Yan S*. 2023. APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response. eLife. 12: e82324.

(9) Li J, Yan S*. 2023. Molecular mechanisms of nucleolar DNA damage checkpoint response. Trends in Cell Biology. 33 (5): 361-364.

(8) Li J, Zhao H, McMahon A, Yan S*. 2022. APE1 assembles biomolecular condensates to promote the ATR-Chk1 DNA damage response in nucleolus. Nucleic Acids Research. 50(18):10503-10525.

(7) Lin Y, Raj J, Li J, Ha A, Hossain MA, Richardson C, Mukherjee P, Yan S*. 2020. APE1 senses DNA single-strand breaks for repair and signaling. Nucleic Acids Research. 48(4):1925-1940.

(6) Ha A, Lin Y, and Yan S*. 2020. A non-canonical role for the DNA glycosylase NEIL3 in suppressing APE1 endonuclease-mediated ssDNA damage. Journal of Biological Chemistry. 295 (41): 14222-14235.

(5) Yan S*. 2019. Resolution of a complex crisis at DNA 3′ termini. Nature Structural & Molecular Biology. 26 (5): 335-336.

(4) Lin Y, Bai L, Cupello S, Hossain MA, Deem B, McLeod M, Raj J, Yan S*. 2018. APE2 promotes DNA damage response pathway from a single-strand break. Nucleic Acids Research. 46 (5): 2479-2494.

(3) Wallace BD, Berman Z,, Mueller GA, Lin Y, Chang T, Andres SN, Wojtaszek JL, DeRose EF, Appel CD, London RE, Yan S*, Williams RS^*. 2017. APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress. PNAS. 114 (2):304-309.

(2) Yan S*, Sorrell M, Berman Z. 2014. Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress. Cellular and Molecular Life Sciences. 71 (20): 3951-3967.

(1) Willis J, Patel Y, Lentz B, Yan S*. 2013. APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. PNAS. 110 (26): 10592-10597.

Click the link for the video (~10 minutes): JoVE-Video

Willis J, DeStephanis D, Patel Y, Gowda V, and Yan S*. 2012. Study of the DNA damage checkpoint using Xenopus egg extracts. Journal of Visualized Experiments. (69): e4449 10.3791/4449. DOI: http://dx.doi.org/10.3791/4449

Click the link for the webinar by Dr. Yan to the NIH DNA Repair Interest Group (~65minutes): Videocast at NIH.