کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8294131 | 1536750 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cytoplasmic p53 contributes to the removal of uracils misincorporated by HIV-1 reverse transcriptase
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
HIV-1 reverse transcriptase (RT) in the cytoplasm of HIV-infected cells efficiently inserts the non-canonical dUTP into the proviral DNA, and extends the dU-terminated DNA. The misincorporation of dUTP leads to mutagenesis, and uracils can down-regulate viral gene expression. However, uracilation might also protect HIV DNA from auto-integration in the cytoplasm. Tumor suppressor p53 protein, exhibiting inherent 3â²â5â² exonuclease activity, provides a potential host-derived repair mechanism during HIV reverse transcription for the misincorporation of various wrong nucleotides, leading to both base-base mismatches and incorporated non-canonical ribonucleotides. Since the presence of proofreading activity is essential for DNA synthesis accuracy, we elucidated the potential involvement of cytoplasmic p53 in the U-editing activities during insertion of dUTP into DNA by recombinant HIV-1 RT (using isogenic p53-proficient and -deficient HCT116â¯cells). The biochemical data show that p53 in cytoplasm can participate through the intermolecular pathway in a dU-damage-associated repair mechanism by its ability to remove preformed 3â²-terminal dUs, thus preventing further extension of 3â² dU-terminated primer during DNA synthesis by HIV-1 RT. The specific depletion of p53 from cytoplasmic lysates of repair-proficient p53-harboring cells reduced this negative effect. Accordingly, the increased abundance of p53 in nutlin-treated cells correlates with enhanced error-correction functions, namely, removal of incorporated uracil. The data substantiate the significance of p53 as a potential proofreader for removal of non-canonical dUTP from HIV DNA, thus preventing the consequences of dUTP misincorporation in cell-type specific infectivity of HIV.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 497, Issue 2, 4 March 2018, Pages 804-810
Journal: Biochemical and Biophysical Research Communications - Volume 497, Issue 2, 4 March 2018, Pages 804-810
نویسندگان
Yossi Saragani, Amnon Hizi, Galia Rahav, Sara Zaouch, Mary Bakhanashvili,