BROAD-SPECTRUM OF INVIVO FORWARD MUTATIONS, HYPERMUTATIONS, AND MUTATIONAL HOTSPOTS IN A RETROVIRAL SHUTTLE VECTOR AFTER A SINGLE REPLICATION CYCLE - DELETIONS AND DELETIONS WITH INSERTIONS

被引:201
作者
PATHAK, VK [1 ]
TEMIN, HM [1 ]
机构
[1] UNIV WISCONSIN,MCARDLE LAB CANC RES,1400 UNIV AVE,MADISON,WI 53706
关键词
plus strand synthesis; RNase H; template switching;
D O I
10.1073/pnas.87.16.6024
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In the preceding paper we described an experiment that determined the in vivo forward mutation rate in a single replication cycle for spleen necrosis virus. In addition to substitutions, frameshifts, and hypermutations, the mutated proviruses contained two classes of deletions. One class of deletions contained short direct repeats at the deletion junctions. Another class of deletions had short stretches of sequences inserted at the deletion junctions. In this report, we describe the deletion mutations, and we present models for their generation. Detailed analysis of two deletions with insertions indicates that these mutations occurred as a result of template switching during plus-strand DNA synthesis. The analysis also indicates that fragments of viral RNA generated by the viral RNase H endonuclease are used as templates and contribute to the sequences inserted at the deletion junctions.
引用
收藏
页码:6024 / 6028
页数:5
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