Title:   
Professor

Institute:
McGill University, Montreal

Department:
Rosalind and Morris Goodman Cancer Research Center

Province:
Quebec

Training:  
Postdoctoral fellow, NIH, Bethesda, Maryland, USA
PhD, McGill University, Montreal, Quebec, Canada
MSc, McGill University, Montreal, Quebec, Canada
BSc, McGill University, Montreal, Quebec, Canada

Research interests:
Regulation of initiation of DNA replication; role of the Ku protein in breast carcinogenesis; comparative analysis of replication origins and their activation in tumor versus normal cells

Recognitions:
University Researcher Award, Programme expérimental de soutien à l'emploi scientifique, Fonds FCAC Ministère de Science et Technologie, Gouvernement du Québec
Scientist Award, Medical Research Council of Canada
Prix DEKA Award for High Technology, Hellenic Board of Trade of Metropolitan Montreal

Research Projects

Project title:
The role of Ku protein in breast tumorigenesis: implications for therapy

Funding period:  
2010-2012

Program:
Operating Grant (Basic Research)

Summary:
All cells must replicate their genetic material (DNA), which is organized into chromosomes. A fundamental component of many normal and disease-related processes is the replication of DNA, whose control occurs at the level of initiation. Dr. Zannis-Hadjopoulos’ laboratory has been studying the regulation of initiation of human DNA replication, using cell cultures. They have been concentrating on studying the DNA sites where replication starts (replication origins) and the factors that are involved, in order to understand how the initiation of replication is regulated. Dr. Zannis-Hadjopoulos’ team previously identified Ku as a protein involved in the initiation of DNA replication. As its expression is deregulated in breast cancer and Ku plays key roles in cell growth and death, they propose to explore its role in breast tumorigenesis and tumor progression, using human cell culture, in order to identify novel therapeutic strategies.

CRS publications:

Landry and Zannis-Hadjopoulos. Classes of autonomously replicating sequences are found among early-replicating monkey DNA. Biochim Biophys. Acta 1088:234-244, 1991

Pearson et al. Plasmids bearing mammalian DNA-replication origin-enriched (ors) fragments initiate semincservative replication in a cell-free system. Biochim Biophys. Acta 1090:156-166, 1991

Shihab-El-Deen et al. Chromosomal localization of a sequence with in vivo activity for initiation of DNA replication. Somat. Cell Molec. Genet. 19:103-109, 1993

Pearson et al. Cruciform DNA binding protein in HeLa cell extracts. Biochemistry 33:14185-14196, 1994

Zannis-Hadjopoulos et al. Autonomous replication in vivo and in vitro of clones spanning the region of the DHFR origin of bidirectional replication (oribeta). Gene 151:273-277, 1994

Todd et al. Deletion analysis of minimal sequence requirements fir aytibiniys replication of ors8, a monkey early-replicating DNA sequence. J. Cell. Biochem. 57:280-289, 1995.

Pearson et al. A novel type of interaction between cruciform DNA and a cruciform binding protein from HeLa cells. The EMBO J. 14:1571-1580, 1995

Steinmetzer et al. Anti-cruciform monoclonal antibody and cruciform DNA interaction. J. Mol. Biol. 254:29-37, 1995.

Pearson et al. Inverted repeats, stem-loops, and cruciforms: significance for initiation of DNA replication. J. Cell. Biochem. 63:1-22, 1996

Tao et al. Differential DNA replication origin activities in human normal skin fibroblast and HeLa cell lines. J. Mol. Biol. 273:509-518

Zannis-Hadjopoulos and Price. Regulatory parameters of DNA replication. Crit. Rev. Euk. Gene Expr. 8:81-106, 1998

Tao et al. Major DNA replication initiation sites in the c-myc locus in human cells. J. Cell. Biochem. 78:442-457, 2000

Rodriguez et al. NAP-2: Histone chaperone function and phosphorylation state through the cell cycle. J. Mol. Biol. 298:225-238, 2000

Alvarez et al. 14-3-3sigma is a cruciform binding protein and associates in vivo with origins of DNA replication. J. Cell. Biochem. 87:194-207, 2002

Callejo et al. The 14-3-3 protein homologues from S. cerevisiae, Bmh1p and Bmh2p, have cruciform DNA-binding activity and associate in vivo with ARS307. J. Biol. Chem. 277:38416-38423, 2002

Novac et al. The human cruciform-binding protein, CBP, is involved in DNA replication and associates in vivo with mammalian replication origins. J. Biol. Chem. 277:11174-11183, 2002

Alvarez et al. Analysis of the cruciform binding activity of recombinant 14-3-3zeta-MBP fusion protein, its heterodimerization profile with endogenous 14-3-3 isoforms, and effect on mammalian DNA replication in vitro. Biochemistry 42:7205-7215, 2003

Price et al. Identification of a cis-element that determines autonomous DNA replication in Eukaryotic cells. J. Biol. Chem. 278:19649-19659, 2003

Rodriguez et al. NAP-2 is part of multi-protein complexes in HeLa cells. J. Cell. Biochem. 93:398-408, 2004

Zannis-Hadjopoulos et al. Eukaryotic replication origin binding proteins. Frontiers Biosci. 9:2133-2143, 2004

Zannis-Hadjopoulos and Price. DNA replication. Encycloped. Of Life Sci., John Wiley & Sons, 2005

Yahyaoui et al. Deletion of the cruciform binding domain in CBP/14-3-3 displays reduced origin binding and initiation of DNA replication in budding yeast. BMC Mol. Biol. 8:27, 2007

Yahyaoui and Zannis-Hadjopoulos.  14-3-3 proteins function in the initiation and elongation steps of DNA replication in Saccharomyces cerevisiae. J. Cell Sci. 122:4419-4426, 2009

Past CRS projects: 
 
2003 Isolation and characterization of mammalian cruciform DNA binding proteins involved in regulation of DNA replication
 
1995 Isolation and characterization of mammalian cruciform DNA binding proteins involved in regulation of DNA replication.
 
1993 Analysis of the role of DNA cruciforms in DNA replication