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!
(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):
(1) 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 (PMCID: PMC7038996; PMID: 31828326)
(2) 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. (PMCID: PMC5861430; PMID: 29361157)
(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. Proceedings of the National Academy of Sciences of the United States of America. 114 (2):304-309. (PMCID: PMC5240719; PMID: 28028224)
(4) 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. (PMCID: PMC4176976; PMID: 24947324)
(5) Willis J§, Patel Y§, Lentz B, Yan S*. 2013. APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proceedings of the National Academy of Sciences of the United States of America. 110 (26): 10592-10597. (PMCID: PMC3696815; PMID: 23754435).
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 PMCID: PMC3514051.
Department of Biological Sciences website: http://biology.uncc.edu/