Joint Mechanisms of genetic and epigenetic stability: Pol Epsilon and beyond Seminar details October 29, 2019, 12:00 pm @ Murray Seminar RoomRoberto Bellelli Host: Constance Alabert / Karim Labib / John Rouse Roberto Bellelli studied medicine in Naples, and first became interested in DNA replication through an internship in the laboratory of Anindya Dutta, at the University of Virginia Medical School. Roberto then returned to Naples to undertake his doctoral work in the group of Francesca Carlomagno, where he discovered a role for the NCOA4 transcriptional coactivator in regulating the activation of DNA replication origins in human cells. Subsequently, Roberto joined the group of Simon Boulton at the Francis Crick institute in London, where he has made two major discoveries during the course of his postdoctoral work. Firstly, Roberto studied mutations in DNA polymerase epsilon that are associated with a form of primordial dwarfism in human patients, and showed that they induce DNA replication stress, abnormal development, and tumourigenesis. Secondly, Roberto found that the two smallest subunits of the DNA polymerase epsilon complex function as a chaperone for histones H3-H4, and help to maintain chromatin integrity during the course of chromosome duplication. Key publications: Bellelli R, Belan O, Pye VE, Clement C, Maslen SL, Skehel JM, Cherepanov P, Almouzni G, Boulton SJ. POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication. Mol Cell. 2018 Oct 4;72,112-126. Bellelli R, Borel V, Logan C, Svendsen J, Cox DE, Nye E, Metcalfe K, O’Connell SM, Stamp G, Flynn HR, Snijders AP, Lassailly F, Jackson A, Boulton SJ. Polε Instability Drives Replication Stress, Abnormal Development, and Tumorigenesis. Mol Cell. 2018 May 17;70(4):707-721. Stingele J, Bellelli R, Alte F, Hewitt G, Sarek G, Maslen SL, Tsutakawa SE,Borg A, Kjær S, Tainer JA, Skehel JM, Groll M, Boulton SJ. Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN. Mol Cell. 2016 Nov 17;64(4):688-703. Bellelli R, Federico G, Matte’ A, Colecchia D, Iolascon A, Chiariello M, Santoro M, De Franceschi L, Carlomagno F. NCOA4 Deficiency Impairs Systemic Iron Homeostasis. Cell Rep. 2016 Jan 26;14(3):411-21. Bellelli R, Castellone MD, Guida T, Limongello R, Dathan NA, Merolla F, Cirafici AM, Affuso A, Masai H, Costanzo V, Grieco D, Fusco A, Santoro M, Carlomagno F. NCOA4 Transcriptional Coactivator Inhibits Activation of DNA Replication Origins. Mol Cell. 2014 Jul 3;55(1):123-37.