ATM-dependent DNA damage surveillance in T-cell development and leukemogenesis: the DSB connection.

Abstract:

:The immune system is capable of recognizing and eliminating an enormous array of pathogens due to the extremely diverse antigen receptor repertoire of T and B lymphocytes. However, the development of lymphocytes bearing receptors with unique specificities requires the generation of programmed double strand breaks (DSBs) coupled with bursts of proliferation, rendering lymphocytes susceptible to mutations contributing to oncogenic transformation. Consequently, mechanisms responsible for monitoring global genomic integrity must be activated during lymphocyte development to limit the oncogenic potential of antigen receptor locus recombination. Mutations in ATM (ataxia-telangiectasia mutated), a kinase that coordinates DSB monitoring and the response to DNA damage, result in impaired T-cell development and predispose to T-cell leukemia. Here, we review recent evidence providing insight into the mechanisms by which ATM promotes normal lymphocyte development and protects from neoplastic transformation.

journal_name

Immunol Rev

journal_title

Immunological reviews

authors

Matei IR,Guidos CJ,Danska JS

doi

10.1111/j.0105-2896.2006.00361.x

keywords:

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

142-58

eissn

0105-2896

issn

1600-065X

pii

IMR361

journal_volume

209

pub_type

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