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SUMMARY:Genome-wide analysis of AID activity and AID-mediated translocatio
 ns in B lymphocytes - Rafael Casellas\, NIH
DTSTART:20110506T151500Z
DTEND:20110506T170000Z
UID:TALK29955@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:B lymphocytes are particularly prone to cancer-promoting trans
 locations as a result of activation-induced cytidine deaminase (AID) expre
 ssion. This enzyme normally diversifies antibody genes by initiating immun
 oglobulin (Ig) class switch recombination and somatic hypermutation. Altho
 ugh AID has a strong preference for targeting the Ig loci\, it also mutate
 s non-Ig genes\, including Bcl6\, Pax5\, miR142\, Pim1\, and c-myc oncogen
 es. Of these\, c-myc is the only one conclusively shown to undergo chromos
 omal translocations because of AID. Yet\, it has been estimated that up to
  5% of activated primary B lymphocytes carry Ig fusions to a large number 
 of unidentified partners1. Consistent with this idea\, we recently charact
 erized thousands of potential AID targets in the B cell genome by means of
  ChIP-Seq technology2. We showed that AID is recruited to promoter proxima
 l sequences of these genes by interacting with Spt53\, an RNA polymerase s
 talling factor. However\, whether any of these new targets undergoes AID-m
 ediated lesions or whether they are substrates of chromosomal translocatio
 ns is unclear. To directly answer these questions we have developed two ne
 w genome-wide strategies that comprehensively map AID-dependent DNA breaks
 \, rearrangements\, and Ig gene translocations in B lymphocytes. In contra
 st to the large number of AID recruiting genes\, our studies uncover ~150 
 targets that are frequently associated with DNA lesions and fuse to recomb
 ining Ig loci upon B cell activation. How chromosome position\, epigenetic
  marks\, and gene transcription contribute to these chromosomal rearrangem
 ents will be discussed.
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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