Department of Cell and Molecular Biology
Faculty, Graduate Program
Our lab is interested in two essential mechanisms that ensure genomic stability in mammalian cells: Protection of chromosome ends. Because of their linear organization the terminal portion of mammalian chromosomes are unstable and can be processed by the DNA damage repair machinery resulting in genomic instability. Specialized nucleoprotein complexes termed telomeres suppress these deleterious events. During the onset of several human pathologies, such as cancer and aging, cells lose the ability to efficiently protect their chromosome ends and thus accumulate high levels of genomic instability. Research in our laboratory aims to elucidate the mechanisms by which telomeres can suppress the DNA damage response in normal cells and how these mechanisms are deregulated in human pathologies. Cell type specific cell fate in response to DNA damage. A complementary approach in the lab is to understand what factors affect the cellular response to telomere deprotection. To this end we use mouse genetics to probe the cellular fate of terminally differentiated as well as multipotent stem cells to telomere deprotection.
Ph.D., Cancer Biology, The Open University in London, 2004
B.S., Molecular Biology, University of Milan, 2000
Lazzerini Denchi E, Sfeir A. Stop pulling my strings - what telomeres taught us about the DNA damage response. Nature reviews Molecular cell biology. 2016;17(6):364-78. Epub 2016/05/12. doi: 10.1038/nrm.2016.43. PubMed PMID: 27165790.
Mateos-Gomez PA, Gong F, Nair N, Miller KM, Lazzerini Denchi E, Sfeir A. (2015) Mammalian Polymerase Theta Promotes Alternative-NHEJ and Suppresses Recombination. Nature. Feb 12;518(7538):254-7. PMID: 25642960
Bartocci C, Diedrich JK, Ouzounov I, Li J, Piunti A, Pasini D, Yates JR 3rd, Lazzerini Denchi E. (2014) Isolation of Chromatin from Dysfunctional Telomeres Reveals an Important Role for Ring1b in NHEJ-Mediated Chromosome Fusions. Cell Rep. 7(4):1320-32. PMCID: PMC4054697
Groocock LM, Nie M, Prudden J, Moiani D, Wang T, Cheltsov A, Rambo RP, Arvai AS, Hitomi C, Tainer JA, Luger K, Perry JJ, Lazzerini Denchi E, Boddy MN. (2014). RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response. EMBO Rep. 15(5):601-8. PMCID: PMC4210088
Okamoto K, Bartocci C, Ouzounov I, Diedrich JK, Yates Iii JR, Lazzerini Denchi E. (2013). A two-step mechanism for TRF2-mediated chromosome-end protection. Nature, 494(7438):502-5. PMCID:PMC3733551
Lazzerini Denchi, E. and de Lange, T. (2007). Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature, 448(7157), 1068-1071.