کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1980042 1539392 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
DNA damage mediated transcription arrest: Step back to go forward
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
DNA damage mediated transcription arrest: Step back to go forward
چکیده انگلیسی


• Stalling of RNA polymerase provokes the formation of R-loops when not resolved might induce genome instability.
• Transcription inhibition induces a strong signal for cell cycle arrest and apoptosis.
• These toxic and mutagenic effects are counteracted by transcription coupled nucleotide excision repair (TC-NER).
• Novel factors in TC-NER and transcription recovery reveal a complex regulation of the DNA damage mediated transcription response by posttranslational modification.

The disturbance of DNA helix conformation by bulky DNA damage poses hindrance to transcription elongating due to stalling of RNA polymerase at transcription blocking lesions. Stalling of RNA polymerase provokes the formation of R-loops, i.e. the formation of a DNA-RNA hybrid and a displaced single stranded DNA strand as well as displacement of spliceosomes. R-loops are processed into DNA single and double strand breaks by NER factors depending on TC-NER factors leading to genome instability. Moreover, stalling of RNA polymerase induces a strong signal for cell cycle arrest and apoptosis. These toxic and mutagenic effects are counteracted by a rapid recruitment of DNA repair proteins to perform transcription coupled nucleotide excision repair (TC-NER) to remove the blocking DNA lesions and to restore transcription. Recent studies have highlighted the role of backtracking of RNA polymerase to facilitate TC-NER and identified novel factors that play key roles in TC-NER and in restoration of transcription. On the molecular level these factors facilitate stability of the repair complex by promotion and regulation of various post-translational modifications of NER factors and chromatin substrate. In addition, the continuous flow of new factors that emerge from screening assays hints to several regulatory levels to safeguard the integrity of transcription elongation after disturbance by DNA damage that have yet to be explored.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 36, December 2015, Pages 28–35
نویسندگان
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