Dr. Huen's major research interest focuses on molecular mechanisms that underlie DNA damage signaling and repair processes. Maintenance of genome stability is key to cell and organismal survival. As such, his laboratory aims to understand the basic but sophisticated protocols that mammalian cells have evolved to protect their genome integrity in face of genotoxic stress. These protocols, generally and collectively referred to as the DNA Damage Response (DDR), involve prompt detection of DNA lesions, propagation of the DNA damage signal, and subsequent execution of appropriate cellular processes, including cell cycle checkpoint and DNA repair. Together, these diverse events ensure faithful inheritance of their genetic material. Importantly, dysregulation of DDR components not only contributes to tumorigenesis, but also predisposes individuals to a host of neurological disorders. His laboratory employs molecular and cell biology techniques to dissect the molecular mechanisms that drive the DDR. By identifying the basic components and unraveling the intimate connections of the DDR protein network, Dr. Huen and his group strives to uncover novel and feasible means via which to detect, treat and eradicate DDR-associated human diseases.
An L, Jiang Y, Ng HH, Man EP, Chen J, Khoo US, Gong Q, Huen MS. Dual-utility NLS drives RNF169-dependent DNA damage responses. Proc Natl Acad Sci U S A. 2017 Apr 4; 114(14): E2872-E2881.
Feng W, Guo Y, Huang J, Deng Y, Zang J, Huen MS. TRAIP regulates fork recovery and progression via PCNA. Cell Discovery, 2016 Jun 28;2:16016.
Ng HM, Wei L, Lan L, Huen MS. The K63-deubiquitylating enzyme BRCC36 limits DNA break processing and repair. J Biol Chem, 2016 Jul 29;291(31):16197-207.
Lau WC, Li Y, Liu Z, Gao Y, Zhang Q, Huen MS. Structure of the human dimeric ATM kinase. Cell Cycle 2016; 15(8): 1117-1124. (pdf)
Huen MS, Chen J. H1 provides the missing link. Cell Res 2016; 26(1):5-6. (pdf)
Guo Y, Feng W, Sy SM, Huen MS. ATM-dependent phosphorylation of the Fanconi anemia protein PALB2 promotes the DNA Damage Response. J Biol Chem 2015; 290: 27545-56.
Lau WC, Li Y, Zhang QF, Huen MS. Molecular architecture of the Ub-PCNA/Pol eta complex bound to DNA. Sci Rep 2015; 5:15759. (pdf)
Hau PM, Deng W, Jia L, Yang J, Tsurumi T, Chiang AK, Huen MS, Tsao SW. Role of ATM in the formation of replication compartment during lytic replication of EBV in nasopharyngeal epithelial cells. J Virol 2015; 89(1):652-68.
Sy SM, Jiang J, O WS, Deng Y, Huen MS. (2013). The ubiquitin specific protease USP34 promotes ubiquitin signaling at DNA double-strand breaks. Nucleic Acids Res. 2013 October; 41(18): 8572–8580. (pdf)
Lok GT, Sy SM, Dong S, Ching YP, Tsao SW, Thomson TM, Huen MS. (2012). Differential regulation of RNF8-mediated Lys48- and Lys63-based poly-ubiquitylation. Nucleic Acids Res; 40(1):196-205. (pdf)
Sy SM, Jiang J, Dong S, Lok GT, Wu J, Cai H, Yeung ES, Huang J, Chen J, Deng Y, Huen MS. (2011). Critical roles of Ring Finger Protein RNF8 in replication stress responses. J Biol Chem; 286: 22355-22361. (pdf)
Deng W, Tsao SW, Mak GW, Tsang CM, Ching YP, Guan XY, Huen MS, Cheung AL.(2011). Impact of G(2) checkpoint defect on centromeric instability. Oncogene; 30(11): 128-9. (pdf)
Sy MS, Chen J, Huen MS. (2010). The 53BP1-EXPAND1 connection in chromatin structure regulation. Nucleus; 1(6):472-4. (pdf)
Huen MS, Sy SM, Leung KM, Ching YP, Tipoe GL, Man C, Dong S, Chen J. (2010). SON is a spliceosome-associated factor required for mitotic progression. Cell Cycle; 9(13): 2679-85. (pdf)
Huen MS, Chen J.(2010). ATM creates a veil of transcriptional silence. Cell; 141:924-6. (pdf)
Santos MA, Huen MS, Jankovic M, Chen H, Lopez-Contreras A, Klein IA, Wong N, Barbancho JL, Fernandez-Capetillo O, Nussenzweig MC, Chen J, Nussenzweig A. (2010). Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8. J Exp Med; 207(5):973-81. (pdf)
Huen MS, Huang J, Leung JW, Sy SM, Leung KM, Ching YP, Tsao SW, Chen J. (2010). Regulation of chromatin architecture by the PWWP domain-containing DNA damage responsive factor EXPAND1. Mol Cell; 37:1-11. (pdf)
Huen MS, Sy SM, Chen J. (2010). BRCA1 and its toolbox for the maintenance of genome integrity. Nat Rev Mol Cell Biol; 11(2):138-48. (pdf)
Huen MS, Chen J. (2010). Assembly of checkpoint and repair machineries at DNA damage sites. Trends Biochem Sci; 35(2):101-8. (pdf)
Sy SM, Huen MS, Chen J. (2009).MRG15 is a novel PALB2 interacting factor involved in homologous recombination. J Biol Chem; 284(32):21127-31. (pdf)
Sy SM, Huen MS, Zhu YY, Chen J. (2009). PALB2 regulates recombinational repair through chromatin association and oligomerization. J Biol Chem; 284(27):18302-10. (pdf)
Sy SM, Huen MS, Chen J. (2009). PALB2 is an integral component of the BRCA complex required for homologous recombination repair. Proc Natl Acad Sci USA; 106(17):7155-60. (pdf)
Huang J, Huen MS, Kim H, Leung CC, Glover JN, Yu X, Chen J. (2009). RAD18 transmits DNA damage signaling to elicit homologous recombination repair. Nat Cell Biol; 11(5):592-603. (pdf)
Wu J, Huen MS, Lu LY, Ye L, Dou Y, Ljungman M, Chen J, Yu X. (2009). Histone ubiquitination associates with BRCA1-Dependent DNA Damage Response. Mol Cell Biol; 29(3):849-60. (pdf)
Huen MS, Chen J. (2008). When loose ends finally meet. Nat Struct Mol Biol;15(12):1241-2. (pdf)
Huen MS, Huang J, Yuan J, Yamamoto M, Akira S, Ashley C, Xiao W, Chen J.(2008). Non-canonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol Cell Biol; 28(19):6104-12. (pdf)
Minter-Dykhouse K, Ward I, Huen MS, Chen J, Zou L. (2008). Distinct versus overlapping functions of MDC1 and 53BP1 in DNA damage response and tumorigenesis. J Cell Bio;181(5):727-35. (pdf)
Huen MS, Sy SM, van Deursen JM, Chen J. (2008). Direct interaction between SET8 and PCNA couples H4-K20 methylation with DNA replication. J Biol Chem;283(17):11073-7. (pdf)
Huen MS, Chen J. (2008). The DNA damage response pathways: at the crossroad of protein modifications. Cell Res; 18(1):8-16. (pdf)
Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J. (2007). RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell; 131(5):901-14. (pdf)