Bin Wang, Ph.D.
Present Title & Affiliation
- DNA damage response
- Genomic instability and Cancer
- BRCA1 signaling
- Ubiquitin signaling
Defects in the ability of cells to properly respond to and repair DNA damage result in genomic instability and underlie many forms of cancer. The goal of our research is to understand how cells respond to DNA damage and safeguard the integrity of the genome.
Cells have evolved a complex sensory network called the DNA damage response (DDR) to respond to genotoxic stress. The DDR coordinates cell cycle regulation, DNA repair, chromatin reorganization and transcription in response to damage. Once DNA damage is sensed, a phosphorylation signaling cascade is initiated by the central DNA damage kinases, ATM and ATR. Recently, a DNA damage induced ubiquitin signaling pathway has also emerged that works together with phosphorylation-dependent signaling to recruit essential repair factors to the sites of DNA damage. Damage-induced ATM/ATR phosphorylation on S139 of histone H2AX directly recruits MDC1 through MDC1ís BRCT domains. MDC1 itself is a substrate of ATM/ATR, and its phosphorylation leads to the recruitment of a ubiquitin E2/E3 ligase RNF8/UBC13 to damage sites. We are seeking to identify additional players in this signaling cascade and investigate the role of each player in the DNA damage repair and signaling, as well as its role in cancer progression.
The RNF8/Ubc13-dependent ubiquitination on the damaged chromatin creates docking sites for BRCA1 complexes. The BRCA1 tumor suppressor is associated with hereditary breast and ovarian cancer and plays critical roles in DNA repair, cell cycle checkpoint control and maintenance of genomic stability. BRCA1 contains two C-terminal BRCT repeats and a N-terminal RING domain that binds BARD1 forming an E3 ubiqutin ligase. Recently we have identified a novel BRCA1 associated protein complex, the Rap80/Abraxas/BRCA1 complex (BRCA1-A complex). In this complex, Abraxas contains a phosphorylated SPxF motif at its C-terminus that associates with the BRCT domain of BRCA1. The BRCA1-A complex also contains a deubiquitination enzyme BRCC36. We are currently investigating how the BRCA1-A complex is involved in BRAC1ís function in breast tumor suppression.
In summary, we are interested in using various biochemical and genetic approaches, such as gene knockouts, mass spectrometry and genetic screens using siRNA libraries, to identify important players in the DNA damage response and define the roles of these proteins in maintaining genomic stability and tumor suppression.
View a compelte list of Dr. Wang's publications.
Department of Genetics Unit 1010
1515 Holcombe Blvd
Houston, TX 77030
Room Number: BSRB S13.8116A
Phone: 713 834-6365
Education & Training
|2000||Baylor College of Medicine, Houston, TX, PHD, Biochemistry and Molecular Biology|
|10/2003-8/2008||Postdoctoral Fellow, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, Dr. Stephen J. Elledge|
|10/2000-10/2003||Postdoctoral Fellow, Baylor College of Medicine, Houston, TX, Dr. Stephen J. Elledge|
Peer-Reviewed Original Research Articles
|1.||Wu Q, Paul A, Su D, Mehmood S, Foo TK, Ochi T, Bunting EL, Xia B, Robinson CV, Wang B, Blundell TL. Structure of BRCA1-BRCT/Abraxas Complex Reveals Phosphorylation-Dependent BRCT Dimerization at DNA Damage Sites. Mol Cell 61(3):434-48, 2/2016. e-Pub 1/2016. PMCID: PMC4747905.|
|2.||Castillo A, Paul A, Sun B, Huang TH, Wang Y, Yazinski SA, Tyler J, Li L, You MJ, Zou L, Yao J, Wang B. The BRCA1-Interacting Protein Abraxas Is Required for Genomic Stability and Tumor Suppression. Cell Rep 8(3):807-17, 8/2014. e-Pub 7/2014. PMCID: PMC4149256.|
|3.||Hu X, Paul A, Wang B. Rap80 protein recruitment to DNA double-strand breaks requires binding to both small ubiquitin-like modifier (SUMO) and ubiquitin conjugates. J Biol Chem 287(30):25510-9, 7/2012. e-Pub 6/2012. PMCID: PMC3408150.|
|4.||Wang B. BRCA1 tumor suppressor network: focusing on its tail. Cell Biosci 2(1):6, 2012. e-Pub 2/2012. PMCID: PMC3315748.|
|5.||Hu X, Kim JA, Castillo A, Huang M, Liu J, Wang B. NBA1/Merit40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36 containing complexes. J Biol Chem 286(13):11734-45, 4/2011. e-Pub 1/2011. PMCID: PMC3064225.|
|6.||Wang B, Hurov K, Hofmann K, Elledge SJ. NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control. Genes Dev 23(6):729-39, 3/2009. PMCID: PMC2661606.|
|7.||Xiao A, Li H, Schecter D, Ahn SH, Fabrizio LA, Erdjument-Bromage H, Ishibe-Murakami S, Wang B, Tempst P, Hofmann K, Patel DJ, Elledge SJ, Allis CD. WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity. Nature 457(7225):57-62, 1/2009. e-Pub 12/2008. PMCID: PMC2854499.|
|8.||Wang B, Elledge SJ. Ubc 13/Rnf8 ubiquitin ligase controls foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc Natl Acad Sci U S A 104(52):20759-63, 12/2007. e-Pub 12/2007. PMCID: PMC2410075.|
|9.||Wang B, Matsuoka S, Ballif BA, Zhang D, Smogorzewska A, Gygi S, Elledge SJ. Abraxas and Rap80 form a BRCA1 protein complex required for the DNA damage response. Science 316(5828):1194-8, 2007. PMID: 17525340.|
|10.||Adams MM, Wang B, Xia Z, Morales JC, Lu X, Donehower LA, Bochar DA, Elledge SJ, Carpenter PB. 53BP1 oligomerization is independent of its methylation by PRMT1. Cell Cycle 4(12):1854-61, 2005. PMID: 16294047.|
|11.||Stewart G, Wang B, Bignell CR, Taylor AM, Elledge SJ. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature 421(6926):961-6, 2/2003. PMID: 12607005.|
|12.||Wang B, Matsuoka S, Carpenter PB, Elledge SJ. 53BP1 a mediator of the DNA damage checkpoint. Science 298(5597):1435-8, 11/2002. PMID: 12364621.|
Last updated: 8/23/2016