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Mechanisms of DNA Double-Strand Break Repair in Hematopoietic Homeostasis and Oncogenesis

  • Sarah A. Maas
  • Lura Brianna Caddle
  • Kevin D. Mills
Chapter

Introduction

Chromosomal instability is a hallmark of cancer associated with many, if not all, tumor types (reviewed in Aplan, 2006; Ferguson and Alt, 2001; Mills et al., 2003) (Fig. 4.1). Structural and numerical chromosomal abnormalities often play key roles in tumorigenesis and can occur as principle lesions in tumor precursor cells. These molecular alterations to the genome occur as a consequence of various exogenous or endogenous insults, producing chromosomal translocations, interstitial deletions, gene amplifications, and other aberrations. While extensive and nonrecurrent chromosomal lesions are associated with many different cancer types, specific characteristic lesions are often associated with given tumors, especially those of hematologic origin (Agarwal et al., 2006; Aplan, 2006; Ferguson and Alt, 2001).

Keywords

Fanconi Anemia Class Switch Recombination Holliday Junction Breakpoint Cluster Region Fanconi Anemia Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations

AID

Activation-induced cytidine deaminase

ALL

Acute lymphoblastic leukemia

AML

Acute myeloid leukemia

ART

Artemis

AT

Ataxia telangiectasia

ATM

Ataxia telangiectasia mutated

ATR

ATM and Rad3 related

B-ALL

B-cell acute lymphoblastic leukemia

BFB

Breakage–fusion–bridge

CHO

Chinese hamster ovary

CML

Chronic myelogenous leukemia

CSR

Class switch recombination

DNA–PKcs

DNA-dependent protein kinase catalytic subunit

DSB

DNA double-strand break

FA

Fanconi anemia

GC

Gene conversion

H2AX

Histone H2A variant X

HR

Homologous recombination

ICL

Interstrand crosslinking

Ig

Immunoglobulin

IgH

Immunoglobulin heavy chain

IR

Ionizing radiation

Lig4

Ligase IV

MDS

Myelodysplastic syndrome

MEF

Mouse embryonic fibroblast

MMC

Mitomycin-C

MRN

Mre11-Rad50-Nbs1 complex

NHEJ

Nonhomologous end joining

Ph

Philadelphia

Pre-T LBL

Pre-T cell lymphoblastic leukemia

RAG

Recombination-activating gene

RPA

Replication protein A

RS

Recombination signal sequences

RS-SCID

Radiation-sensitive SCID

SCE

Sister chromatid exchange

SCID

Severe combined immunodeficiency

SDSA

Synthesis-dependent strand annealing

SHM

Somatic hypermutation

SSA

Single-strand annealing

ssDNA

Single-stranded DNA

T-ALL

T-cell acute lymphoblastic leukemia or lymphoma

TCR

T-cell receptor

TOPOIII

Topoisomerase III

XLF

XRCC4-like factor

Notes

Acknowledgments

We thank Dr. Sophie La Salle for critical review of this manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Sarah A. Maas
    • 1
  • Lura Brianna Caddle
  • Kevin D. Mills
  1. 1.The Jackson LaboratoryUSA

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