DNA double-strand break repair

Introduction

Double strand breaks & single-strand gaps in damaged DNA are efficiently repaired by mechanisms associated with recombination. Double strand breaks are created by agents such as ionizing radiation, some chemotherapeutic agents & in certain recombination reactions. In yeast, double strand breaks are repaired by homologous recombination, but this is not the case in higher eukaryotes.

Damaged bases & segments of single-stranded DNA can be produced by agents causing double strand breaks such as ionizing radiation. Thus processing of DNA ends must ensue before ligation of the severed DNA strands occurs.

V(D)J site-specific recombination generates the diversity in developing B-cells & T cells. It results from the action of lymphoid-restricted recombination-activation genes RAG1 & RAG2 in connection with a ubiquitously expressed system that completes the recombination. This ubiquitously expressed system is the DNA double-strand break repair system.

Inadequate repair of double-strand breaks can result in a variety of genetic lesions, including small deletions, translocations resulting from non homologous rearrangements & loss of large segments of the genome.

More general terms

• DNA repair

More specific terms

• homologous recombination
• non-homologous end joining (NHEJ)

Additional terms

• double stranded DNA-dependent protein kinase (DNA-PK)
• NAD+ ADP-ribosyltransferase or poly ADP-ribose polymerase