Roberto Jose Pezza, Ph.D.
Cell Cycle & Cancer Biology Research Program
Everybody knows you can break your arm, but most people are unaware that you can break your DNA, too. And fewer still know that DNA can be repaired.
Deoxyribonucleic acid, or DNA, is a string of four different chemicals that make up the library of you. The order of chemicals in your DNA is the determining factor in the color of your hair, how tall you can grow and how your body makes proteins and other chemicals. And you don’t just have one piece of DNA – there’s a copy in almost every cell in your body.
Damage to DNA can cause or contribute to a number of diseases, and in my lab, we’re studying how breaks and repairs at different points in life can affect health. DNA that is cut or malformed in the embryonic stage can cause birth defects and lead to Down syndrome or Turner syndrome. If DNA is damaged after birth, it can sometimes cause cancer.
We’re studying a system that repairs a specific kind of DNA cut and how some repairs are good and others cause problems. By understanding how the system works, we hope to better diagnose disease and find ways to treat or prevent birth defects and some kinds of cancer.
B.S., National University of Cordoba, Argentina, 1997
M.S., National University of Cordoba, Argentina, 1997
Ph.D., National University of Cordoba, Argentina, 2002
Research Fellow, National Institutes of Health, Bethesda, MD, 2007-2009
Honors and Awards
1997 Scholarship, National University of Cordoba, State of Cordoba Scientific Research Council (CONICOR), Argentina
1998-2000 Fellowship (for initial training in research), National Research Council (CONICET), Argentina
2000-2002 Fellowship, National Research Council (CONICET) Argentina
2002-2004 Research Excellence Award, National Universities and National Educational Council, Argentina
2003-2007 Visiting Fellow, National Institutes of Health, Bethesda, MD
2007-2009 Research Fellow, National Institutes of Health
2007 Fellows Award for Research Excellence, National Institutes of Health
Joined OMRF Scientific Staff in 2009.
Chromosome aneuploidies are the leading cause of infertility and birth defects in humans. They result from errors in the segregation of homologous chromosomes (HCs) during gametogenesis. The proper segregation of chromosomes is ensured by meiotic homolog recombination (HR). It begins with the introduction of DNA double-strand breaks (DSBs) followed by their repair using the intact DNA of a HCs as template. This leads to a temporal association of the HCs in pairs that ensures their orderly segregation to opposite poles of dividing nuclei so that each gamete receives one (and only one) homolog of each pair. The homologs that fail to synapse segregate randomly, having 50% chances to go into the same daughter cell. Consequently, mutations that reduce or abolish recombination are invariably associated with gross abnormalities in chromosome segregation. An estimated 10 to 30% of fertilized human eggs have the wrong number of chromosomes resulting in at least 5% of conceptions being aneuploid. Most of them abort before term making aneuploidy the leading known cause of pregnancy loss. Those who survive face devastating consequences, including developmental disabilities and mental retardation.
The field of homologous recombination faces exciting challenges. One of the biggest tests will be to connect the dots between the biochemical function of proteins involved in HR and their in vivo role.
My laboratory studies the bases involved in the repair of DSBs and HCs synapses in mouse. We use a combination of different approaches ranging from the reconstruction of in vitro systems using purified proteins to the generation of genetically modified mice. Our goal is to uncover the fundamental molecular mechanisms regulating the process of homologous recognition and the proper segregation of HCs.
Bugreev DV, Huang F, Mazina OM, Pezza RJ, Voloshin ON, Daniel Camerini-Otero R, Mazin AV. HOP2-MND1 modulates RAD51 binding to nucleotides and DNA. Nat Commun 5:4198, 2014. [Abstract]
Moktan H, Guiraldelli MF, Eyster CA, Zhao W, Lee CY, Mather T, Camerini-Otero RD, Sung P, Zhou DH, Pezza RJ. Solution Structure and DNA-binding properties of the winged helix domain of the meiotic recombination HOP2 protein. J Biol Chem 289:14682-14691, 2014. [Abstract]
Pezza RJ, Voloshin ON, Volodin AA, Boateng KA, Bellani MA, Mazin AV, Camerini-Otero RD. The dual role of HOP2 in mammalian meiotic homologous recombination. Nucleic Acids Res 42:2346-2357, 2014. [Abstract]
Bisig CG, Guiraldelli MF, Kouznetsova A, Scherthan H, Hoog C, Dawson DS, Pezza RJ. Synaptonemal complex components persist at centromeres and are required for homologous centromere pairing in mouse spermatocytes. PLoS Genet 8:e1002701, 2012. [Abstract]
Pezza RJ, Camerini-Otero RD, Bianco PR. Hop2-Mnd1 condenses DNA to stimulate the synapsis phase of DNA strand exchange. Biophys J 99:3763-3772, 2010. [Abstract]
Bugreev DV, Pezza RJ, Mazina OM, Voloshin ON, Camerini-Otero RD, Mazin AV. The resistance of DMC1 D-loops to dissociation may account for the DMC1 requirement in meiosis. Nat Struct Mol Biol 18:56-60, 2011. [Abstract]
Pezza RJ, Voloshin ON, Vanevski F, Camerini-Otero RD. Hop2/Mnd1 acts on two critical steps in Dmc1-promoted homologous pairing. Genes Dev 21:1758-1766, 2007. [Abstract]
Bannister LA, Pezza RJ, Donaldson JR, de Rooij DG, Schimenti KJ, Camerini-Otero RD, Schimenti JC. A dominant, recombination-defective allele of Dmc1 causing male-specific sterility. PLoS Biol 5:e105, 2007. [Abstract]
Pezza RJ, Petukhova GV, Ghirlando R, Camerini-Otero RD. Molecular activities of meiosis-specific proteins Hop2, Mnd1, and the Hop2-Mnd1 complex. J Biol Chem 281:18426-18434, 2006. [Abstract]
Petukhova GV, Pezza RJ, Vanevski F, Ploquin M, Masson JY, Camerini-Otero RD. The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination. Nat Struct Mol Biol 12:449-453, 2005. [Abstract]
Cell Cycle and Cancer Biology Research Program, MS 48
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-6467
Fax: (405) 271-7312
Simon Terzyan, Ph.D.
Associate Staff Scientist
Michel Guiraldelli, Ph.D.
Assistant Staff Scientist
Craig Eyster, Ph.D.
Associate Staff Scientist
Emma Lee, Ph.D.
Rodrigo Orlandini De Castro, Ph.D.
Network & Computer Systems Administrator