Nonhomologous DNA end joining in cell-free systems

被引:60
作者
Labhart, P [1 ]
机构
[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1999年 / 265卷 / 03期
关键词
DSB repair; nonhomologous DNA end joining; DNA-dependent protein kinase; ligation; in vitro assay; illegitimate recombination; DNA-protein interaction;
D O I
10.1046/j.1432-1327.1999.00805.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Double strand DNA. breaks are usually caused by ionizing radiation and radiomimetic drugs, but can also occur under normal physiological conditions during double strand break-induced recombination, such as the rearrangement of T-cell receptor and immunoglobulin genes during lymphoid development or the mating type switching in yeast. The main repair mechanism for double strand breaks in higher eukaryotes is nonhomologous DNA end joining (NHEJ), which modifies and ligates the two DNA ends without the help of extensive base-pairing interactions for alignment. Defects in double strand break repair are associated with radiosensitivity, predisposition to cancer and immunodeficiency syndromes, and the analysis of the underlying mutations has lead to the identification of several proteins involved in NHEJ. However, these genetic studies have yielded little information on the mechanism of NHEJ, and while some of the protein factors identified possess the expected enzymatic or DNA-binding activities, the precise role of others remains unclear. Systems for cell-free NHEJ have been available for over 10 years, but the biochemical analysis of NHEJ has lagged behind the genetic analysis, and not a single protein factor required for NHEJ has been identified by biochemical purification and reconstitution of NHEJ activity. Here I review the current status of in vitro systems for NHEJ, summarize the results obtained and information gained, and discuss the outlook for biochemical approaches to study NHEJ.
引用
收藏
页码:849 / 861
页数:13
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