Matthews Adam G W, Oettinger Marjorie A
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Adv Exp Med Biol. 2009;650:16-31. doi: 10.1007/978-1-4419-0296-2_2.
V(D)J recombination is initiated by the lymphoid specific proteins RAG1 and RAG2, which together constitute the V(D)J recombinase. However, the RAG 1/2 complex can also act as a transposase, inserting the broken DNA molecules generated during V(D)J recombination into an unrelated piece of DNA. This process, termed RAG transposition, can potentially cause insertional mutagenesis, chromosomal translocations and genomic instability. This review focuses on the mechanism and regulation of RAG transposition. We first provide a brief overview of the biochemistry of V(D)J recombination. We then discuss the discovery of RAG transposition and present an overview of the RAG transposition pathway. Using this pathway as a framework, we discuss the factors and forces that regulate RAG transposition.
V(D)J重排由淋巴特异性蛋白RAG1和RAG2启动,它们共同构成V(D)J重组酶。然而,RAG 1/2复合物也可作为转座酶,将V(D)J重排过程中产生的断裂DNA分子插入到一段不相关的DNA中。这一过程称为RAG转座,可能会导致插入诱变、染色体易位和基因组不稳定。本综述聚焦于RAG转座的机制与调控。我们首先简要概述V(D)J重排的生物化学。然后讨论RAG转座的发现,并概述RAG转座途径。以该途径为框架,我们讨论调控RAG转座的因素和作用力。