Parallel Session
Chair(s)
  • Mirjam Van der Burg, Netherlands
  • Beata Wolska-Kuśnierz, Poland
Room
Bozar
Date
19.09.2019, Thursday
Session Time
11:00 - 12:30
Parallel Session No Topic Needed

WISKOTT-ALDRICH SYNDROME: A GENOME INSTABILITY IMMUNE DISORDER

Lecture Time
11:00 - 11:30
Presenter
  • Yatin M. Vyas, United States of America
Room
Bozar
Date
19.09.2019, Thursday
Session Time
11:00 - 12:30
Presentation Topic
No Topic Needed

Abstract

Abstract Body

DNA damage-mediated genome instability is a contributing factor in the causation of human diseases, including neurodegeneration, immunological disorders, and cancer. Understanding how cells prevent and manage DNA damage is highly significant. Pathological accumulation of R loops, transcription-linked 3 nucleic-acid structure consisting of a RNA:DNA hybrid and a displaced single-strand DNA (ssDNA), causes genomic instability upon its cleavage into DNA double strand breaks (DSBs). Using a PID disease model of human Wiskott-Aldrich syndrome (WAS), we recently discovered an essential nuclear role of WASp, the protein deficient in WAS, in preventing R loop-mediated DNA DSBs in T lymphocytes. Others discovered impaired repair of DSBs from deficient homology-directed repair (HDR) in WAS B cells. Together, the evidence suggest that WAS T and B lymphocytes are poorly-equipped to both prevent and resolve DSBs sustained from the genomic stress of transcription, ionizing-radiation, and chemotherapy. We recently uncovered an additional, essential function of WASp in coordinating the cell-protective Golgi dispersal response (GDR) induced by DNA DSBs in human T and B cells. These studies have dramatically expanded the field of play for WASp, from historically an Arp2/3-mediated modifier of actin in the cytoplasm to now supporting a novel, essential function(s) of stabilizing the genome in the nucleus.

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Parallel Session No Topic Needed

HUMAN TELOMERE BIOLOGY DISORDERS AND NEW INSIGHTS INTO NHP2 DEFICIENCY

Lecture Time
11:30 - 12:00
Presenter
  • Patrick Revy, France
Room
Bozar
Date
19.09.2019, Thursday
Session Time
11:00 - 12:30
Presentation Topic
No Topic Needed

Abstract

Abstract Body

Telomeres are nucleoprotein structures at the end of chromosomes. The telomerase complex, constituted of the catalytic subunit TERT, the RNA matrix hTR, and several cofactors including the H/ACA box ribonucleoproteins (RNP) Dyskerin, NOP10, GAR1, NAF1, and NHP2, regulates telomere length. In humans, inherited defects in telomere length maintenance are responsible for a wide spectrum of clinical premature aging manifestations including pulmonary fibrosis (PF), dyskeratosis congenita (DC), bone marrow failure (BMF), Immunodeficiency and predisposition to cancer. NHP2 mutations have been so far reported only in two patients with DC. Here, we report the first case of Høyeraal-Hreidarsson syndrome (HH), the severe form of DC, caused by biallelic missense mutations in NHP2. Additionally, we identified three unrelated patients with PF carrying NHP2 heterozygous mutations. Strikingly, one of these patients acquired a somatic mutation in the promoter of TERT that likely conferred a selective advantage in a subset of blood cells. Lastly, we demonstrate that a functional deficit of human NHP2 affects ribosomal RNA biogenesis. Together, our results broaden the functional consequences and clinical spectrum of NHP2 deficiency.

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Parallel Session No Topic Needed

RECQL4: ON THE CROSSROADS OF IMMUNE DEFICIENCY AND CANCER: RTS AND RAPADILINO

Lecture Time
12:00 - 12:30
Presenter
  • Isabelle Meyts, Belgium
Room
Bozar
Date
19.09.2019, Thursday
Session Time
11:00 - 12:30
Presentation Topic
No Topic Needed