Specificity of End Resection Pathways for Double-Strand Break Regions Containing Ribonucleotides and Base Lesions

Simple item page
dc.contributor.authorDaley, James M.
dc.contributor.authorTomimatsu, Nozomi
dc.contributor.authorHooks, Grace
dc.contributor.authorWang, Weibin
dc.contributor.authorMiller, Adam S.
dc.contributor.authorXue, Xiaoyu
dc.contributor.authorNguyen, Kevin A.
dc.contributor.authorKaur, Hardeep
dc.contributor.authorWilliamson, Elizabeth
dc.contributor.authorMukherjee, Bipasha
dc.contributor.authorHromas, Robert
dc.contributor.authorBurma, Sandeep
dc.contributor.authorSung, Patrick
dc.date.accessioned2020-07-22T13:58:06Z
dc.date.available2020-07-22T13:58:06Z
dc.date.issued2020-06
dc.description.abstractDNA 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.
dc.description.departmentChemistry and Biochemistry
dc.formatText
dc.format.extent13 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationDaley, J. M., Tomimatsu, N., Hooks, G., Wang, W., Miller, A. S., Xue, X., Nguyen, K. A., Kaur, H., Williamson, E., Mukherjee, B., Hromas, R., Burma, S., & Sung, P. (2020). Specificity of end resection pathways for double-strand break regions containing ribonucleotides and base lesions. Nature Communications, 11(1), pp. 1-12.
dc.identifier.doihttps://doi.org/10.1038/s41467-020-16903-4
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/10877/12138
dc.language.isoen
dc.publisherSpringer
dc.rights.holder© The Author(s) 2020.
dc.rights.licenseThis work is licensed under a Creative Commons Attribution 4.0 International License.
dc.sourceNature Communications, 2020, Vol. 11, No. 1, pp. 1-12.
dc.subjectDNA
dc.subjectdouble-strand break repair
dc.subjectribonucleotides
dc.subjectChemistry and Biochemistry
dc.titleSpecificity of End Resection Pathways for Double-Strand Break Regions Containing Ribonucleotides and Base Lesions
dc.typeArticle

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
document(16).pdf
Size:
3.22 MB
Format:
Adobe Portable Document Format
Description:
Download

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.54 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

College of Science and Engineering