The research interests of our laboratory include the mechanisms of DNA damage response, chromatin remodeling, epigenetic modifications, and their roles in tumorigenesis. As a principle investigator, I have extensive expertise and motivation necessary to successfully carry out the research projects that are supported by National Institute of Health and other funding agencies. The research conducted in my laboratory results a number of manuscripts published in leading journals. Six trainees from my laboratory have successfully become independent investigators, established their own laboratories, and generated scientific contributions in cancer research field.
Postdoctoral fellow positions are available to work in the areas of DNA damage response and chromatin biology. The approaches we take range from mammalian cell culture, molecular biology, biochemistry to mouse genetics. A strong background in molecular and cellular biology is essential. Experience with protein affinity purification or mouse model analysis is desirable. We are seeking candidates who are self-motivated and career-oriented.
1. Kim, H., Chen, J. * and Yu, X. * (2007). Ubiquitin-binding protein RAP80 mediates BRCA1- dependent DNA damage responses. Science, 316, 1202-1205. (* co-corresponding authors). This study demonstrates RAP80 as a major ubiquitin-binding protein that participates in DNA damage response.
2. Liu, Z., Wu, J., and Yu, X. (2007). CCDC98 targets BRCA1 to DNA damage sites. Nature Structural and Molecular Biology, 14, 716-720. We identified CCDC98 as an important functional partner of BRCA1 that recruits BRCA1 to DNA lesions.
3. Huen, M., Grant, R., Manke, I., Minn, K., Yu, X.*, Yaffe, M.* and Chen, J.* (2007). The E3 ubiquitin ligase RNF8 propagates the DNA damage signal via an ubiquitin-dependent signaling pathway. Cell, 131, 901-914. (* co-corresponding authors) We and others identified RNF8 as a key enzyme to initiate ubiquitination cascade in response to DNA damage.
4. Zhang, F., Ma, J., Wu, J., Ye, L., Cai, H., Xia, B. * and Yu, X. * (2009) PALB2 links BRCA1 and BRCA2 in the DNA damage response. Current Biology, 19: 524-529. (* co-corresponding authors) We found that BRCA1 and BRCA2 function in a same molecular pathway during DNA damage response. This novel finding has been highlighted in Science (324: 602-603)
5. Lu, L.Y., Wu, J., Ye, L. Gavrilina, G.B., Saunders, T.L. and Yu, X. (2010). RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis. Developmental Cell. 18, 371-384. We demonstrated the functional significance of histone ubiquitination in chromatin remodeling during spermatogenesis.
6. Zhang, F. and Yu, X. (2011). WAC, a partner of RNF20/40 complex, regulates histone H2B ubiquitination and gene transcription. Molecular Cell. 41, 384-397. We identified a novel enzyme complex that catalyzes histone H2B ubiquitination.
7. Wu, J., Chen, Y., Lu, L.Y., Wu, Y., Paulsen, M.T., Ljungman, M., Ferguson, D.O. and Yu, X. (2011). Chfr and RNF8 synergistically regulate ATM activation. Nature Structural and Molecular Biology. 18: 761-768. We demonstrate a novel molecular mechanism by which protein ubiquination cascade regulates DNA damage response.
8. Chen, Q., Chen, Y., Bian, C., Fujiki, R. and Yu, X. (2013) TET2 promotes histone O-GlcNacylation during gene transcription. Nature 493:561-564. Our study reveals a unique double-epigenetic modification in gene transcription. This novel finding, for the first time, demonstrates a functional interaction between DNA demethylation and histone O-GlcNAcylation in gene transcription. This novel finding has been highlighted in
Nature Reviews Molecular Cell Biology (14:64-65).
9. Ma, T., Chen, Y., Zhang, F., Yang, C-Y., Wang, S. and Yu, X. (2013) RNF111-dependent neddylation activates DNA damage-induced ubiquitination. Molecular Cell. 49: 897-907. Our study reveals a novel epigenetic modification, namely histone neddylation.
10. Li, M. and Yu, X. (2013) Function of BRCA1 in the DNA damage response is mediated by ADP-ribosylation. Cancer Cell. 23: 693-704. We demonstrate that the BRCT domain is a novel ADP-ribose binding domain. The study may not only open a new avenue in DNA damage response, but also explain a molecular mechanism by which PARP inhibitors specifically kill breast tumor cells bearing BRCA1 mutations. It may have a major impact for future breast and ovarian cancer treatment. This novel finding has been highlighted in
Cancer Cell (23:565-567).
11. Lu, L, Korakavi, G., Kuang, H. and Yu, X. (2013) Distinct DNA damage responses on male meiotic sex chromosomes. Nature Communications. 3015. This study reveals a unique phenomenon of DNA damage repair in male germ cells.
12. Li, M., Lu, L., Yang, C., Wang, S. and Yu, X. (2013) The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response. Genes&Development. 27: 1752-1768. We identified the BRCT and FHA domains as novel poly(ADP-riose)-binding domains, which facilitates to understand the basic molecular mechanism of DNA damage repair.
13. Chen, Y., Chen, Q., McEachin, R.C., Cavalcoli J.D. and Yu, X. (2014) H2A.B facilitates transcription elongation at methylated CpG loci. Genome Research.24:570-579. We demonstrate the function of H2A.B, a special mammalian histone H2A variant, in gene transcription. This novel finding has been highlighted in Nature Reviews Molecular Cell Biology (15:222).
14. Zhang, F., Chen, Y., Li, M. and Yu, X. (2014) The OB-fold motif is a poly(ADP-ribose)-binding domain that mediates DNA damage response. Proceedings of the National Academy of Sciences. 111:7278-7283. Our study reveals the OB-fold motif as another “reader” of poly(ADP-ribose). This work together with our previous studies opens a new avenue in DNA damage-induced signal transduction pathway.
15. Bian, C., Chen, Q. and Yu, X. (2015) ZNF644 and WIZ regulate the G9a/GLP complex for gene repression. eLife. 08168. This study reveals a novel molecular mechanism by which G9a regulates epigenetic modifications and transcription.