Kanamitsu Kyoichiro, Ikeda Shogo
Department of Biochemistry, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
J Nucleic Acids. 2010 Sep 16;2010:450926. doi: 10.4061/2010/450926.
DNA base excision repair (BER) accounts for maintaining genomic integrity by removing damaged bases that are generated endogenously or induced by genotoxic agents. In this paper, we describe the roles of enzymes functioning in the early steps of BER in fission yeast. Although BER is an evolutionarily conserved process, some unique features of the yeast repair pathway were revealed by genetic and biochemical approaches. AP sites generated by monofunctional DNA glycosylases are incised mainly by AP lyase activity of Nth1p, a sole bifunctional glycosylase in yeast, to leave a blocked 3' end. The major AP endonuclease Apn2p functions predominantly in removing the 3' block. Finally, a DNA polymerase fills the gap, and a DNA ligase seals the nick (Nth1p-dependent or short patch BER). Apn1p backs up Apn2p. In long patch BER, Rad2p endonuclease removes flap DNA containing a lesion after DNA synthesis. A UV-specific endonuclease Uve1p engages in an alternative pathway by nicking DNA on the 5' side of oxidative damage. Nucleotide excision repair and homologous recombination are involved in repair of BER intermediates including the AP site and single-strand break with the 3' block. Other enzymes working in 3' end processing are also discussed.
DNA碱基切除修复（BER）通过去除内源性产生或由基因毒性剂诱导产生的受损碱基来维持基因组完整性。在本文中，我们描述了裂殖酵母中在BER早期步骤中发挥作用的酶的作用。尽管BER是一个进化上保守的过程，但通过遗传和生化方法揭示了酵母修复途径的一些独特特征。单功能DNA糖基化酶产生的AP位点主要由酵母中唯一的双功能糖基化酶Nth1p的AP裂解酶活性切割，留下一个封闭的3'末端。主要的AP核酸内切酶Apn2p主要在去除3'末端封闭物方面发挥作用。最后，DNA聚合酶填补缺口，DNA连接酶封闭切口（Nth1p依赖性或短补丁BER）。Apn1p作为Apn2p的后备。在长补丁BER中，Rad2p核酸内切酶在DNA合成后去除含有损伤的翼片DNA。紫外线特异性核酸内切酶Uve1p通过在氧化损伤的5'侧切割DNA参与一条替代途径。核苷酸切除修复和同源重组参与包括AP位点和带有3'末端封闭物的单链断裂在内的BER中间体的修复。还讨论了在3'末端加工中起作用的其他酶。
