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Specificity of end resection pathways for double-strand break regions containing ribonucleotides and base lesions
by
Williamson, Elizabeth
, Sung, Patrick
, Miller, Adam S.
, Mukherjee, Bipasha
, Wang, Weibin
, Kaur, Hardeep
, Hooks, Grace
, Hromas, Robert
, Burma, Sandeep
, Nguyen, Kevin A.
, Daley, James M.
, Tomimatsu, Nozomi
, Xue, Xiaoyu
in
13/106
/ 13/89
/ 631/337/1427/2122
/ 631/337/1427/2190
/ 631/337/149
/ 631/45/147
/ 82/29
/ 82/83
/ Blotting, Western
/ Cell Line, Tumor
/ Deoxyribonucleic acid
/ Depletion
/ DNA
/ DNA Breaks, Double-Stranded
/ DNA damage
/ DNA Glycosylases - genetics
/ DNA repair
/ DNA Repair Enzymes - genetics
/ DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics
/ Double-strand break repair
/ Exodeoxyribonucleases - genetics
/ Fluorescent Antibody Technique
/ Guanine
/ Homologous recombination
/ Homologous Recombination - genetics
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Hybrids
/ Lesions
/ multidisciplinary
/ Nuclease
/ OGG1 protein
/ Recombination, Genetic - genetics
/ RecQ Helicases - genetics
/ Repair
/ Ribonuclease
/ Ribonucleic acid
/ Ribonucleotides
/ Ribonucleotides - genetics
/ Ribonucleotides - metabolism
/ RNA
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Science
/ Science (multidisciplinary)
/ Unwinding
/ Yeast
2020
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Specificity of end resection pathways for double-strand break regions containing ribonucleotides and base lesions
by
Williamson, Elizabeth
, Sung, Patrick
, Miller, Adam S.
, Mukherjee, Bipasha
, Wang, Weibin
, Kaur, Hardeep
, Hooks, Grace
, Hromas, Robert
, Burma, Sandeep
, Nguyen, Kevin A.
, Daley, James M.
, Tomimatsu, Nozomi
, Xue, Xiaoyu
in
13/106
/ 13/89
/ 631/337/1427/2122
/ 631/337/1427/2190
/ 631/337/149
/ 631/45/147
/ 82/29
/ 82/83
/ Blotting, Western
/ Cell Line, Tumor
/ Deoxyribonucleic acid
/ Depletion
/ DNA
/ DNA Breaks, Double-Stranded
/ DNA damage
/ DNA Glycosylases - genetics
/ DNA repair
/ DNA Repair Enzymes - genetics
/ DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics
/ Double-strand break repair
/ Exodeoxyribonucleases - genetics
/ Fluorescent Antibody Technique
/ Guanine
/ Homologous recombination
/ Homologous Recombination - genetics
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Hybrids
/ Lesions
/ multidisciplinary
/ Nuclease
/ OGG1 protein
/ Recombination, Genetic - genetics
/ RecQ Helicases - genetics
/ Repair
/ Ribonuclease
/ Ribonucleic acid
/ Ribonucleotides
/ Ribonucleotides - genetics
/ Ribonucleotides - metabolism
/ RNA
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Science
/ Science (multidisciplinary)
/ Unwinding
/ Yeast
2020
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Specificity of end resection pathways for double-strand break regions containing ribonucleotides and base lesions
by
Williamson, Elizabeth
, Sung, Patrick
, Miller, Adam S.
, Mukherjee, Bipasha
, Wang, Weibin
, Kaur, Hardeep
, Hooks, Grace
, Hromas, Robert
, Burma, Sandeep
, Nguyen, Kevin A.
, Daley, James M.
, Tomimatsu, Nozomi
, Xue, Xiaoyu
in
13/106
/ 13/89
/ 631/337/1427/2122
/ 631/337/1427/2190
/ 631/337/149
/ 631/45/147
/ 82/29
/ 82/83
/ Blotting, Western
/ Cell Line, Tumor
/ Deoxyribonucleic acid
/ Depletion
/ DNA
/ DNA Breaks, Double-Stranded
/ DNA damage
/ DNA Glycosylases - genetics
/ DNA repair
/ DNA Repair Enzymes - genetics
/ DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics
/ Double-strand break repair
/ Exodeoxyribonucleases - genetics
/ Fluorescent Antibody Technique
/ Guanine
/ Homologous recombination
/ Homologous Recombination - genetics
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Hybrids
/ Lesions
/ multidisciplinary
/ Nuclease
/ OGG1 protein
/ Recombination, Genetic - genetics
/ RecQ Helicases - genetics
/ Repair
/ Ribonuclease
/ Ribonucleic acid
/ Ribonucleotides
/ Ribonucleotides - genetics
/ Ribonucleotides - metabolism
/ RNA
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Science
/ Science (multidisciplinary)
/ Unwinding
/ Yeast
2020
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Specificity of end resection pathways for double-strand break regions containing ribonucleotides and base lesions
Journal Article
Specificity of end resection pathways for double-strand break regions containing ribonucleotides and base lesions
2020
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Overview
DNA double-strand break repair by homologous recombination begins with nucleolytic resection of the 5’ DNA strand at the break ends. Long-range resection is catalyzed by EXO1 and BLM-DNA2, which likely have to navigate through ribonucleotides and damaged bases. Here, we show that a short stretch of ribonucleotides at the 5’ terminus stimulates resection by EXO1. Ribonucleotides within a 5’ flap are resistant to cleavage by DNA2, and extended RNA:DNA hybrids inhibit both strand separation by BLM and resection by EXO1. Moreover, 8-oxo-guanine impedes EXO1 but enhances resection by BLM-DNA2, and an apurinic/apyrimidinic site stimulates resection by BLM-DNA2 and DNA strand unwinding by BLM. Accordingly, depletion of OGG1 or APE1 leads to greater dependence of DNA resection on DNA2. Importantly, RNase H2A deficiency impairs resection overall, which we attribute to the accumulation of long RNA:DNA hybrids at DNA ends. Our results help explain why eukaryotic cells possess multiple resection nucleases.
DNA double-strand break repair by homologous recombination initiates with nucleolytic resection of the 5’ DNA strand at the break ends. Here, the authors reveal that the lesion context influences the action and efficiency of the long range resection factors EXO1 and BLM-DNA2.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/89
/ 82/29
/ 82/83
/ DNA
/ DNA Repair Enzymes - genetics
/ DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics
/ Exodeoxyribonucleases - genetics
/ Fluorescent Antibody Technique
/ Guanine
/ Homologous Recombination - genetics
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Hybrids
/ Lesions
/ Nuclease
/ Recombination, Genetic - genetics
/ Repair
/ Ribonucleotides - metabolism
/ RNA
/ Saccharomyces cerevisiae - genetics
/ Saccharomyces cerevisiae - metabolism
/ Science
/ Yeast
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