Höss M, Robins P, Naven T J, Pappin D J, Sgouros J, Lindahl T
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK.
EMBO J. 1999 Jul 1;18(13):3868-75. doi: 10.1093/emboj/18.13.3868.
Mammalian DNA polymerases alpha and beta lack 3' exonuclease activity and are unable to edit errors after DNA synthesis. However, editing exonucleases can be functions of separate polypeptides. We isolated a widely distributed DNA-specific 3' exonuclease from rabbit liver nuclei, sequenced tryptic peptides by mass spectrometry, and identified the corresponding human open reading frame. The protein expressed from the cloned human sequence exhibits 3' exonuclease activity. The human clone shares sequence homology with the editing function of the Escherichia coli DNA polymerase III holoenzyme, i.e., the DnaQ/MutD protein, and weakly with the editing 3' exonuclease domain of eukaryotic DNA polymerase epsilon. The gene maps to human chromosome 3p21.2-21.3. In a reconstituted human DNA repair system containing DNA polymerase beta and DNA ligase III-XRCC1, accurate rejoining of a 3' mismatched base residue at a single-strand break is dependent on addition of the exonuclease.
哺乳动物的DNA聚合酶α和β缺乏3'核酸外切酶活性，无法在DNA合成后校正错误。然而，校正核酸外切酶可能是独立多肽的功能。我们从兔肝细胞核中分离出一种广泛分布的DNA特异性3'核酸外切酶，通过质谱法对胰蛋白酶肽段进行测序，并鉴定出相应的人类开放阅读框。从克隆的人类序列表达的蛋白质具有3'核酸外切酶活性。该人类克隆与大肠杆菌DNA聚合酶III全酶的校正功能（即DnaQ/MutD蛋白）具有序列同源性，与真核生物DNA聚合酶ε的校正3'核酸外切酶结构域的同源性较弱。该基因定位于人类染色体3p21.2 - 21.3。在一个包含DNA聚合酶β和DNA连接酶III - XRCC1的重组人类DNA修复系统中，单链断裂处3'错配碱基残基的准确重新连接依赖于核酸外切酶的添加。
