Dana Branzei
Dana Branzei
affiliation: IFOM-FIRC Institute of Molecular Oncology
research area(s): Molecular Biology, Genetics And Genomics
Course: Molecular Medicine: Molecular Oncology and Computational Biology
University/Istitution: Università di Milano, UNIMI-SEMM
I was born in Iasi, the capital city of Romanian Moldavia. I came to IFOM in 2005 after working for several years in Japan at Tohoku University in Sendai, and at RIKEN Institute in Wako. In IFOM, I initially worked as Staff Scientist with Marco Foiani, Scientific Director of the Institute, on cell cycle control and genome stability. In 2008, I became Head of a new research program on DNA repair at IFOM. Among my contributions to the field of DNA repair, I characterized the role of sumoylation in protecting genes against cancer- causing alterations, and uncovered a crosstalk between ubiquitylation and sumoylation in promoting damage tolerance during replication.
Our lab studies the DNA repair mechanisms that operate in eukaryotic cells, particularly during replication, and the regulatory pathways that coordinate their usage. We have uncovered important roles for the replication checkpoint, CDK, Ubiquitin and SUMO-mediated modifications in promoting DNA damage tolerance events.

DNA synthesis is frequently associated with nucleotide misincorporation, slippage at repetitive sequences, and aberrant transitions at replication forks. These events often result in the formation of single or double strand breaks, which can trigger recombination and endanger the stability of the chromosomes if not appropriately repaired.

When replication occurs in the presence of a damaged template, repriming downstream of the lesion generates gaps that can be filled in by using different strategies. One mechanism (referred to as template switch) is essentially error-free and uses the undamaged information of the sister duplex to bypass the DNA lesion. This resembles a homologous recombination reaction and leads to the formation of transient X-shaped chromosome structures. If left unresolved, however, these molecules can be potentially cleaved by nucleases and trigger recombination. We can detect these DNA molecules by using a combination of techniques, mostly based on the analysis of replication intermediates. The RecQ helicase Sgs1/BLM plays an important role in the resolution of these structures, and we have previously shown that Ubc9 and Mms21 dependent sumoylation controls this process. Sgs1/BLM is sumoylated but in an Mms21-independent fashion indicating that there may be other factors that act in concert with Sgs1/BLM to promote the dissolution of these X-shaped intermediates.

The DNA replication machinery as well as most of the DNA repair factors and the DNA damage response pathways are conserved from yeast to humans. In the lab, we are using the yeast Saccharomyces cerevisiae, chicken B-cell lines, DT-40, and human cells. The budding yeast is a good model system that helps us identify and characterize in molecular detail the mechanisms promoting DNA repair and replication fork transactions. Some of our findings are presently extended in chicken DT40 cells, which are also genetically amenable. DT40 cells spend more than 60% of the cell cycle time in S phase, and are particularly suitable for studies in post replication repair. Furthermore, chromosome instability can be directly assessed by performing mitotic chromosome analysis. Well-conserved factors that appear to impact on genome integrity are tested in human cells for their role in replication, recombination, and the DNA damage response.
1) Dana Branzei (2011). Ubiquitin family modifications and template switching. FEBS Lett., 2011, doi:10.1016/j.febslet.2011.04.053.

2) Dana Branzei (2011). The three SMC sisters. Nature Reviews Molecular Cell Biology (6), 343.

3) Fabio Vanoli, Marco Fumasoni, Barnabas Szakal, Laurent Maloisel, Dana Branzei (2010) Replication and recombination factors contributing to recombination-dependent bypass of DNA lesions by template switch. PLoS Genet, 6(11):e1001205.

4) Koyi Choi, Barnabas Szakal, Yu-Hung Chen, Dana Branzei, and Xiaolan Zhao (2010). The Smc5/6 Complex and Esc2 Influence Multiple Replication-associated Recombination Processes in Saccharomyces cerevisiae. Mol Biol Cell, 21 (13), 2306-2314.

5) Dana Branzei and Marco Foiani (2010). Maintaining genome stability at the replication fork. Nature Reviews Molecular Cell Biology 11, 208-219.

6) Dana Branzei and Marco Foiani (2010). Leaping forks at inverted repeats. Genes and Development, 24 (1), 5-9.

7) Yu-Hung Chen, Koyi Choi, Barnabas Szakal, Jacqueline Arenz, Vladimir Yong-Gonzales, Dana Branzei, and Xiaolan Zhao (2009). Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. PNAS 106(50), 21252-21257.

8) Dana Branzei and Marco Foiani (2009). The checkpoint response to replication stress. DNA Repair, (9), 1038-1046.

9) Julie Sollier, Robert Driscoll, Federica Castellucci, Marco Foiani, Stephen P. Jackson, and Dana Branzei (2009). The S. cerevisiae Esc2 and Smc5-6 proteins promote sister chromatid junction mediated intra-S repair. Mol Biol Cell (6), 1671-1682.

10) Kara A. Bernstein, Erika Shor, Ivana Sunjevaric, Marco Fumasoni, Rebecca C. Burgess, Marco Foiani, Dana Branzei, Rodney Rothstein (2009). Sgs1 function in the repair of DNA replication intermediates is separable from its role in homologous recombinational repair. EMBO Journal (7), 915-925.

11) Dana Branzei, Fabio Vanoli, and Marco Foiani (2008). SUMOylation regulates Rad18-mediated template switch. Nature 456 (7224), 915-920.

12) Rodrigo Bermejo, Dana Branzei, Marco Foiani (2008). Cohesion by topology: sister chromatids interlocked by DNA. Genes and Development 17, 2297-2301.

13) Dana Branzei and Marco Foiani (2008). Regulation of DNA repair throughout the cell cycle. Nature Reviews Molecular Cell Biology 9, 297-308.

14) Dana Branzei and Marco Foiani (2007). Template Switching: from replication fork repair to genome rearrangements. Cell 131, 1228-1230.

15) Dana Branzei and Marco Foiani (2007). RecQ helicases queing with Srs2 to disrupt Rad51 filaments and suppress recombination. Genes and Development 21, 3019-3026.

16) Dana Branzei and Marco Foiani (2007). Interplay of replication checkpoints and repair proteins at stalled replication forks. DNA Repair 6, 994-1003.

17) Dana Branzei, Julie Sollier, Giordano Liberi, Xiaolan Zhao, Daisuke Maeda, Masayuki Seki, Takemi Enomoto, Kunihiro Ohta, and Marco Foiani (2006). Ubc9- and Mms21- mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell 127, 509-522.

18) Dana Branzei and Marco Foiani (2006). The Rad53 signal transduction pathway: replication fork stabilization, DNA repair, and adaptation. Experimental Cell Research, 312 (14), 2654-2659.

19) Dana Branzei and Marco Foiani (2005). The DNA damage response at the replication fork. Curr Opin in Cell Biol., 6, 568-575.
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