HU protein of Escherichia coli has a role in the repair of closely opposed lesions in DNA.
Closely opposed lesions form a unique class of DNA damage that is generated by ionizing radiation. Improper repair of closely opposed lesions could lead to the formation of double strand breaks that can result in increased lethality and mutagenesis. In vitro processing of closely opposed lesions was studied using double-stranded DNA containing a nick in close proximity opposite to a dihydrouracil. In this study we showed that HU protein, an Escherichia coli DNA-binding protein, has a role in the repair of closely opposed lesions. The repair of dihydrouracil is initiated by E. coli endonuclease III and processed via the base excision repair pathway. HU protein was shown to inhibit the rate of removal of dihydrouracil by endonuclease III only when the DNA substrate contained a nick in close proximity opposite to the dihydrouracil. In contrast, HU protein did not inhibit the subsequent steps of the base excision repair pathway, namely the DNA synthesis and ligation reactions catalyzed by E. coli DNA polymerase and E. coli DNA ligase, respectively. The nick-dependent selective inhibition of endonuclease III activity by HU protein suggests that HU could play a role in reducing the formation of double strand breaks in E. coli.
Hashimoto
Mitsumasa
M
Department of Radiation Oncology, Emory University, Atlanta, Georgia 30303, USA.
Imhoff
Barry
B
Ali
Md Moshi
MM
Kow
Yoke W
YW
D001426:Bacterial Proteins / Q000494:pharmacology / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D004256:DNA Polymerase I / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000494:pharmacology / Q000502:physiology*; D004926:Escherichia coli / Q000737:chemistry*; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D014498:Uracil / Q000031:analogs & derivatives* / Q000378:metabolism; D029867:Xenopus Proteins
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; C040330:histone-like protein HU, bacteria; C007419:dihydrouracil; D014498:Uracil; D004247:DNA; D004256:DNA Polymerase I; D005090:Exodeoxyribonucleases; C020133:exodeoxyribonuclease III; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus