BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:The function and execution of RTEL1 activities at vertebrate telom
 eres - Dr Simon Boulton\, DNA damage Response Laboratory\, London Research
  Institute
DTSTART:20140627T151500Z
DTEND:20140627T170000Z
UID:TALK52779@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Regulator of telomere length 1 (RTEL1) is an essential Fe-S de
 pendent DNA helicase that regulates homologous recombination\, disassemble
 s telomere (T)-loops and suppresses telomere fragility to maintain the int
 egrity of the genome. The emergence of RTEL1 variants that confer increase
 d susceptibility to high-grade Glioma\, Astrocytomas and Glioblastomas has
  highlighted the importance of RTEL1 in human cancers. Mutations in RTEL1 
 have also been implicated in Hoyerall-Hreidarsson syndrome (HHS)\, a sever
 e form of the bone marrow failure and cancer predisposition disorder\, Dys
 keratosis Congenita. We previously reported that RTEL1 binds to the replis
 ome via a PIP-box dependent interaction with PCNA. Disruption of the RTEL1
 -PCNA interaction in mice compromised genome-wide and telomere replication
 \, and accelerated the onset of tumourigenesis in p53 deficient animals. U
 nexpectedly\, the RTEL1-PCNA interaction was found to be dispensable for T
 -loop disassembly\, which suggested the existence of a distinct mechanism 
 for recruiting RTEL1 to telomeres. Indeed\, we have discovered that RTEL1 
 is recruited to telomeres via an S-phase specific interaction with the she
 lterin component TRF2. We proceeded to identify a single point mutation wi
 thin TRF2 that abrogates the interaction with RTEL1 and phenocopies the Rt
 el1 null phenotype. Finally\, we demonstrated that the RTEL1-TRF2 interact
 ion is compromised by the R1264H mutation in RTEL1\, which is causal for H
 HS and exists at a carrier frequency of 1 in 100 within the Ashkenazi Jew 
 population. These results define a clinically important interaction betwee
 n RTEL1 and TRF2\, which is critical for the timely disassembly of T-loops
  during S-phase of the cell cycle. \n\n\n•	Barber LJ\, Youds JL\, Ward J
 D\, McIlwraith M\, O’Neil NJ\, Petalcorin MIR\, Collis SJ\, Martin JS\, 
 Cantor SB\, Auclair M\, Tissenbaum H\, West SC\, Rose AM & Boulton SJ (200
 8). RTEL1 maintains genomic stability by suppressing homologous recombinat
 ion. Cell. 135:261-71.\n•	Youds JL\, Mets D\, McIlwraith MJ\, Martin JS\
 , Ward JD\, O’Neil NJ\, Rose AM\, West SC\, Meyer B & Boulton SJ  (2010)
  RTEL-1 enforces meiotic crossover interference and homeostasis. Science\,
  327:1254-8.\n•	Vannier J-B\, Petalcorin MIR\, Pavicic-Kaltenbrunner V\,
  Ding H & Boulton SJ (2012). RTEL1 dismantles T-loops and counteracts telo
 meric G4-DNA to maintain telomere integrity. Cell 149:795-806.\n•	Vannie
 r JB\, Sandhu S\, Petalcorin MIR\, Wu X\, Nabi Z\, Ding H & Boulton SJ (20
 13). RTEL1 is a replisome-associated helicase that promotes genome and tel
 omere replication. Science\, 342: 239-242. \n•	Vannier J-B\, Sarek G & B
 oulton SJ (2014). RTEL1: functions of a disease-associated helicase. Trend
 s in Cell Biology\, 10.1016/j.tcb.2014.01.004. \n\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
END:VEVENT
END:VCALENDAR