Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Cell. 2013 Feb 21;49(4):623-31. doi: 10.1016/j.molcel.2012.11.029. Epub 2013 Jan 3.

53BP1 alters the landscape of DNA rearrangements and suppresses AID-induced B cell lymphoma.

Author information

1
Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065, USA.

Abstract

Deficiencies in factors that regulate the DNA damage response enhance the incidence of malignancy by destabilizing the genome. However, the precise influence of the DNA damage response on regulation of cancer-associated rearrangements is not well defined. Here we examine the genome-wide impact of tumor protein P53-binding protein 1 (53BP1) deficiency in lymphoma and translocation. While both activation-induced cytidine deaminase (AID) and 53BP1 have been associated with cancer in humans, neither AID overexpression nor loss of 53BP1 is sufficient to produce malignancy. However, the combination of 53BP1 deficiency and AID deregulation results in B cell lymphoma. Deep sequencing of the genome of 53BP1(-/-) cancer cells and translocation capture sequencing (TC-Seq) of primary 53BP1(-/-) B cells revealed that their chromosomal rearrangements differ from those found in wild-type cells in that they show increased DNA end resection. Moreover, loss of 53BP1 alters the translocatome by increasing rearrangements to intergenic regions.

PMID:
23290917
PMCID:
PMC3658150
DOI:
10.1016/j.molcel.2012.11.029
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center