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Agnel SfeirAssistant Professor, Department of Cell Biology
Research SummaryThe linearity of chromosomes creates two major problems for eukaryotic cells: the end replication problem and the end protection problem. The former stems from the inherent inability of the replication machinery to fully duplicate linear templates. The latter refers to the propensity of linear chromosome ends to be recognized as DNA double stranded breaks. To surmount both problems, cells use telomeres, the specific nucleoprotein complexes that are essential to ensure genomic stability and promote cellular survival. In mammalian cells, telomeres consist of long tracts of repetitive DNA sequences (TTAGGG) that are bound by a specialized six-subunit protein complex termed shelterin. Telomeres are replenished by telomerase, a reverse transcriptase that is active in the germ line and during early embryonic development. Normal human somatic cells lack the activity of telomerase and gradually loose telomeric repeats during progressive division cycles until they ultimately undergo cellular senescence. Our lab is mainly interested in understanding the basic mechanism that leads to telomere length resetting. In particular, we rely on nuclear reprograming as a platform to identify factors that regulate telomere length. A second area of interest to us is to understand how telomere dynamics impact stem cell function and leads to tumorigenesis, using the mouse as a model organism.
Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination
Mateos-Gomez, Pedro A; Gong, Fade; Nair, Nidhi; Miller, Kyle M; Lazzerini-Denchi, Eros; Sfeir, Agnel. Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination. Nature. 2015 Feb;518(7538):254-257 (1463292)
Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?
Sfeir, Agnel; Symington, Lorraine S. Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated Pathway?. Trends in biochemical sciences. 2015 Sep;:?-? (1794592)
ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres
Tong, Adrian S; Stern, J Lewis; Sfeir, Agnel; Kartawinata, Melissa; de Lange, Titia; Zhu, Xu-Dong; Bryan, Tracy M. ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres. Cell reports. 2015 Nov;13(8):1633-1646 (1907572)
Nontelomeric Role for Rap1 in Regulating Metabolism and Protecting against Obesity
Yeung, Frank; Ramirez, Cristina M; Mateos-Gomez, Pedro A; Pinzaru, Alexandra; Ceccarini, Giovanni; Kabir, Shaheen; Fernandez-Hernando, Carlos; Sfeir, Agnel. Nontelomeric Role for Rap1 in Regulating Metabolism and Protecting against Obesity. Cell reports. 2013 Jun;3(6):1847-1856 (415092)
53BP1 regulates DSB repair using Rif1 to control 5' end resection
Zimmermann, Michal; Lottersberger, Francisca; Buonomo, Sara B; Sfeir, Agnel; de Lange, Titia. 53BP1 regulates DSB repair using Rif1 to control 5' end resection. Science. 2013 Feb;339(6120):700-704 (232802)