Parsons Jason L, Kavli Bodil, Slupphaug Geir, Dianov Grigory L
MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, UK.
Biochemistry. 2007 Apr 3;46(13):4158-63. doi: 10.1021/bi0622569. Epub 2007 Mar 10.
5-Hydroxyuracil (5-OHU) in DNA, arising during endogenous DNA damage and caused by ionizing radiation, is removed by the base excision repair pathway. However, in addition to base lesions, ionizing radiation also generates DNA single-strand breaks (SSBs). When these DNA lesions are located in the proximity of each other, this may result in a profound effect on both repair of the damaged base and the SSB. We therefore examined the repair of DNA substrates containing 5-OHU lesions in the proximity of the 3'-end of a SSB. We found that SSB repair by DNA ligase IIIalpha and DNA polymerase beta is impaired by the presence of the nearby 5-OHU lesion, indicating the requirement for a DNA glycosylase which would be able to remove 5-OHU before SSB repair. Subsequently, we found that although both SMUG1 and NEIL1 are able to excise 5-OHU lesions located in the proximity of the 3'-end of a DNA SSB, NEIL1 is more efficient in the repair of these DNA lesions.
DNA中的5-羟基尿嘧啶（5-OHU）产生于内源性DNA损伤且由电离辐射引起，可通过碱基切除修复途径去除。然而，除了碱基损伤外，电离辐射还会产生DNA单链断裂（SSB）。当这些DNA损伤彼此靠近时，这可能会对受损碱基和SSB的修复产生深远影响。因此，我们研究了在SSB 3'-末端附近含有5-OHU损伤的DNA底物的修复情况。我们发现，附近存在5-OHU损伤会损害DNA连接酶IIIα和DNA聚合酶β对SSB的修复，这表明需要一种能够在SSB修复之前去除5-OHU的DNA糖基化酶。随后，我们发现尽管SMUG1和NEIL1都能够切除位于DNA SSB 3'-末端附近的5-OHU损伤，但NEIL1在修复这些DNA损伤方面更有效。
