Wang Laboratory

Genomic stability

Our Aim

Our Interest

Our Team

Our Projects

1. The function of DNA damage response molecules [ATM, ATR, TopBP1, and the MRE11/RAD50/NBS1 complex] in DNA repair pathways, cell cycle checkpoint and DNA replication, focusing on the pathologies of neuronal disorders and neurodegeneration, as well as tumourigenesis.
2. The interaction of post-translational modifications mediated by poly(ADP-ribosyl)ation, phosphorylation and epigenetic modifications in DNA repair, DNA replication and genomic stability, and its impact on tissue homeostasis, neuronal loss and the brain size determination. The involved proteins include PARPs, PARG, ATR-CHK1, MCPH genes (mutated in human primary microcephaly syndromes), TopBP1 and HAT complexes.
3. The role of DNA damage response and DNA repair in the maintenance and ageing of stem/progenitor cells.

Our Tools

1. Cellular and molecular studies:
   • DNA damage response and repair assays (Western blotting, DRGFP assay, live cell imaging, immunofluorescence analysis, etc)
   • Cell cycle checkpoint activation and cell cycle progression
   • DNA replication and DNA fibres assay
   • Cytogenetic analysis
   • Immunological analysis and V(D)J recombination assays
   • Chromatin immuno-precipitation (ChIP)
   • Protein dynamics
   • Interaction of post-translational modifications
   • Generation of MEF cell lines by retroviral transduction
   • Apoptosis and necrosis assays
2. Neurogenesis analyses in vitro and in vivo:
   • In vitro neurosphere cultures
   • In vivo neuroprogenitor cell cycle assays
   • DNA damage and repair assays in vivo
   • Live cell imaging of neocortical cultures and cells
   • In utero electroporations and manipulations in vivo
   • In situ hybridization
3. Mouse genetics and modeling:
   • Conventional and conditional (or inducible) gene targeting in ES cells and other cell types
   • Generation and characterization of knock-out, knock-in and transgenic mouse models
   • Manipulation of mouse embryos, oocyte injection, blastocyst injection
   • Histopathological analysis of animal models

Selected publications

• Min WK, Wang ZQ (2009) Poly(ADP)-Ribose) Glycohydrolase (PARG) and its therapeutic potential. Frontiers Biosci. 14, 1619-26. [PubMed]
• Baranes K, Raz-Prag D, Nitzan A, Galron R, Ashery-Padan R, Rotenstreich Y, Assaf Y, Shiloh Y, Wang ZQ, Barzilai A (2009) Conditional inactivation of the NBS1 gene in the mouse central nervous system leads to neurodegeneration and disorganization of the visual system. Exp Neurol. 218(1), 24-32. [PubMed]
• Meyer-Ficca ML, Lonchar J, Credidio C, Ihara M, Li Y, Wang ZQ, Meyer RG (2009) Disruption of poly(ADP-Ribose) homeostasis affects spermiogenesis and sperm chromatin integrity in mice. Biol. Reprod. 81(1), 46-55. [PubMed]
• Anisimov V, Piskunova TS, Yurova MN, Ovsjannikov AI, Semenchenko AN, Zabezhinski MA, Popovich IG, Wang ZQ (2008) Deficiency in poly(ADP-ribose) polymerase-1 (PARP-1) accelerates aging and spontaneous carcinogenesis in mice. Curr Gerontol Geriatr Res. 2008:754190. [PubMed]
• Assaf Y, Galron R, Shapira I, Nitzan A, Blumenfeld-Katzir T, Solomon AS, Holdengreber V, Wang ZQ, Shiloh Y, Barzilai A (2008) MRI evidence of white matter damage in a mouse model of Nijmegen Breakage Syndrome. Exp Neurol. 209(1), 181-191.
• Tong WM, Yang YG, Cao WH, Galendo D, Frappart L, Shen Y, Wang ZQ (2007) Poly(ADP-ribose) polymerase-1 plays a role in suppressing mammary tumourigenesis in mice. Oncogene. 26, 3857-3867. [PubMed]
• Murr R, Loizou JI, Yang YG, Cuenin C, Li H, Wang ZQ, Herceg Z (2006) Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nat Cell Biol. 8, 91-99. [PubMed]
• Yang YG, Saidi A, Frappart PO, Min W, Barrucand C, Dumon-Jones V, Michelon J, Herceg Z, Wang ZQ (2006) Conditional deletion of Nbs1 in murine cells reveals its role in branching repair pathways of DNA double-strand breaks. EMBO J. 25, 5527-5538. [PubMed]
• Cuzzocrea S, Di Paola R, Mazzon E, Cortes U, Genovese T, Muià C, Li W, Xu W, Li JH, Zhang J, Wang ZQ (2005) PARG activity mediates intestinal injury induced by splanchnic artery occlusion and reperfusion. FASEB J. 19, 558-566. [PubMed]
• Frappart PO, Tong WM, Demuth I, Radovanovic I, Herceg Z, Aguzzi A, Digweed M, Wang ZQ (2005) An essential function for NBS1 in the prevention of ataxia and cerebellar defects. Nat Med. 11, 538-544. [PubMed]
• Nakanishi K, Yang YG, Pierce AJ, Taniguchi T, Digweed M, D'Andrea AD, Wang ZQ, Jasin M (2005) Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Proc Natl Acad Sci USA.102, 1110-1115. [PubMed]
• Demuth I, Frappart PO, Hildebrand G, Melchers A, Lobitz S, Stöckl L, Varon R, Herceg Z, Sperling K, Wang ZQ, Digweed M (2004) DAn inducible null mutant murine model of Nijmegen breakage syndrome proves the essential function of NBS1 in chromosomal stability and cell viability. Hum Mol Genet. 13, 2385-2397. [PubMed]
• Zong WX, Ditsworth D, Bauer DE, Wang ZQ, Thompson CB (2004) Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. 18, 1272-1282. [PubMed]
• Dumon-Jones V, Frappart PO, Tong WM, Sajithlal G, Hulla W, Schmid G, Herceg Z, Digweed M, Wang ZQ. (2003) Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Cancer Res. 63, 7263-7269. [PubMed]
• Herceg Z, Hulla W, Gell D, Cuenin C, Lleonart M, Jackson S, Wang ZQ. (2001) Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression. Nat Genet. 29, 206-211. [PubMed]