REPAIR AND MISREPAIR OF SITE-SPECIFIC DNA DOUBLE-STRAND BREAKS BY HUMAN CELL-EXTRACTS

被引:52
作者
GANESH, A [1 ]
NORTH, P [1 ]
THACKER, J [1 ]
机构
[1] MRC,DIV CELL & MOLEC BIOL,RADIOBIOL UNIT,DIDCOT OX11 0RD,OXON,ENGLAND
来源
MUTATION RESEARCH | 1993年 / 299卷 / 3-4期
关键词
REPAIR; INVITRO; MISREPAIR; DELETION; DIRECT REPEATS; HUMAN CELL EXTRACTS;
D O I
10.1016/0165-1218(93)90101-I
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The rejoining by human cell extracts of a double-strand break induced by endonuclease treatment at one of several sites within a small DNA molecule was studied. Rejoining was found at each of 8 sites tested, but the rejoin efficiency varied with the nature of the break (e.g., breaks with cohesive ends were rejoined more efficiently than blunt-ended breaks). Extracts from primary and immortalized cell lines, as well as those from individuals with ataxia telangiectasia (A-T), showed the same pattern of relative rejoin efficiencies. However, mis-rejoining varied with the cell extract used, and was particularly elevated with two immortalized A-T cell lines. Mixing experiments showed that the mis-rejoining property of extracts could act in a semi-dominant fashion, depending on the individual efficiencies of the component extracts. The mis-rejoin mechanism involved deletion at sites of short direct repeats at various distances from the initial break site. A model of deletion formation (the strand-exposure and repair model) is restated to explain the sequence repeat dependence found, and is compared to models of homologous DNA recombination.
引用
收藏
页码:251 / 259
页数:9
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