Pathways that suppress programmed DNA breaks from progressing to chromosomal breaks and translocations.
Guarding the genome against internal and external assaults requires the coordinated interaction of multiple cellular networks to sense, respond to, and repair breaks in chromosomal DNA. Both external factors such as ionizing radiation or internal events like oxidative damage can cause DNA double stranded breaks (DSBs). DSBs are also part of the normal lymphocyte developmental program where they are an integral element of the mechanisms that generate a diverse immune repertoire in the context of V(D)J and immunoglobulin heavy chain (IgH) class switch recombination (CSR). DSBs initiate a cascade of cellular events that direct cells to pause and properly repair potentially lethal chromosomal breaks. Errors in the repair of both general and lymphocyte-specific DSBs can lead to oncogenic chromosomal translocations . Here, we review recent advances in understanding factors and protein complexes involved in the response to DNA DSBs with a focus on the B lymphocyte specific process of CSR.
Franco
Sonia
S
Howard Hughes Medical Institute, The Children's Hospital Boston, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Alt
Frederick W
FW
Manis
John P
JP
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D019457:Chromosome Breakage; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D042822:Genomic Instability; D006657:Histones / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008214:Lymphocytes; D016393:Lymphoma, B-Cell / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D017346:Protein Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C064658:RAG-1 protein; C576324:ATM protein, human; C576325:Atm protein, mouse; C475961:gamma-H2AX protein, mouse