HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution

Yair Dorsett; Yanjiao Zhou; Anthony T. Tubbs; Bo Ruei Chen; Caitlin Purman; Baeck Seung Lee; Rosmy George; Andrea L. Bredemeyer; Jiang yang Zhao; Erica Sodergen; George M. Weinstock; Nathan D. Han; Alejandro Reyes; Eugene M. Oltz; Dale Dorsett; Ziva Misulovin; Jacqueline E. Payton; Barry P. Sleckman

doi:10.1016/j.molcel.2014.10.024

HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution

Yair Dorsett, Yanjiao Zhou, Anthony T. Tubbs, Bo Ruei Chen, Caitlin Purman, Baeck Seung Lee, Rosmy George, Andrea L. Bredemeyer, Jiang yang Zhao, Erica Sodergen, George M. Weinstock, Nathan D. Han, Alejandro Reyes, Eugene M. Oltz, Dale Dorsett, Ziva Misulovin, Jacqueline E. Payton, Barry P. Sleckman

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

The structure of broken DNA ends is a critical determinant of the pathway used for DNA double-strand break (DSB) repair. Here, we develop an approach involving the hairpin capture of DNA end structures (HCoDES), which elucidates chromosomal DNA end structures at single-nucleotide resolution. HCoDES defines structures of physiologic DSBs generated by the RAG endonuclease, as well as those generated by nucleases widely used for genome editing. Analysis of G1 phase cells deficient in H2AX or 53BP1 reveals DNA ends that are frequently resected to form long single-stranded overhangs that can be repaired by mutagenic pathways. In addition to 3' overhangs, many of these DNA ends unexpectedly form long 5' single-stranded overhangs. The divergence in DNA end structures resolved by HCoDES suggests that H2AX and 53BP1 may have distinct activities in end protection. Thus, the high-resolution end structures obtained by HCoDES identify features of DNA end processing during DSB repair.

Original language	English
Pages (from-to)	808-818
Number of pages	11
Journal	Molecular cell
Volume	56
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2014.10.024
State	Published - Dec 18 2014

Access to Document

10.1016/j.molcel.2014.10.024

Cite this

Dorsett, Y., Zhou, Y., Tubbs, A. T., Chen, B. R., Purman, C., Lee, B. S., George, R., Bredemeyer, A. L., Zhao, J. Y., Sodergen, E., Weinstock, G. M., Han, N. D., Reyes, A., Oltz, E. M., Dorsett, D., Misulovin, Z., Payton, J. E., & Sleckman, B. P. (2014). HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution. Molecular cell, 56(6), 808-818. https://doi.org/10.1016/j.molcel.2014.10.024

@article{204262158c6c463195616a394ac87404,

title = "HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution",

abstract = "The structure of broken DNA ends is a critical determinant of the pathway used for DNA double-strand break (DSB) repair. Here, we develop an approach involving the hairpin capture of DNA end structures (HCoDES), which elucidates chromosomal DNA end structures at single-nucleotide resolution. HCoDES defines structures of physiologic DSBs generated by the RAG endonuclease, as well as those generated by nucleases widely used for genome editing. Analysis of G1 phase cells deficient in H2AX or 53BP1 reveals DNA ends that are frequently resected to form long single-stranded overhangs that can be repaired by mutagenic pathways. In addition to 3' overhangs, many of these DNA ends unexpectedly form long 5' single-stranded overhangs. The divergence in DNA end structures resolved by HCoDES suggests that H2AX and 53BP1 may have distinct activities in end protection. Thus, the high-resolution end structures obtained by HCoDES identify features of DNA end processing during DSB repair.",

author = "Yair Dorsett and Yanjiao Zhou and Tubbs, {Anthony T.} and Chen, {Bo Ruei} and Caitlin Purman and Lee, {Baeck Seung} and Rosmy George and Bredemeyer, {Andrea L.} and Zhao, {Jiang yang} and Erica Sodergen and Weinstock, {George M.} and Han, {Nathan D.} and Alejandro Reyes and Oltz, {Eugene M.} and Dale Dorsett and Ziva Misulovin and Payton, {Jacqueline E.} and Sleckman, {Barry P.}",

note = "Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",

year = "2014",

month = dec,

day = "18",

doi = "10.1016/j.molcel.2014.10.024",

language = "English",

volume = "56",

pages = "808--818",

journal = "Molecular cell",

issn = "1097-2765",

number = "6",

}

Dorsett, Y, Zhou, Y, Tubbs, AT, Chen, BR, Purman, C, Lee, BS, George, R, Bredemeyer, AL, Zhao, JY, Sodergen, E, Weinstock, GM, Han, ND, Reyes, A, Oltz, EM, Dorsett, D, Misulovin, Z, Payton, JE & Sleckman, BP 2014, 'HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution', Molecular cell, vol. 56, no. 6, pp. 808-818. https://doi.org/10.1016/j.molcel.2014.10.024

TY - JOUR

T1 - HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution

AU - Dorsett, Yair

AU - Zhou, Yanjiao

AU - Tubbs, Anthony T.

AU - Chen, Bo Ruei

AU - Purman, Caitlin

AU - Lee, Baeck Seung

AU - George, Rosmy

AU - Bredemeyer, Andrea L.

AU - Zhao, Jiang yang

AU - Sodergen, Erica

AU - Weinstock, George M.

AU - Han, Nathan D.

AU - Reyes, Alejandro

AU - Oltz, Eugene M.

AU - Dorsett, Dale

AU - Misulovin, Ziva

AU - Payton, Jacqueline E.

AU - Sleckman, Barry P.

PY - 2014/12/18

Y1 - 2014/12/18

N2 - The structure of broken DNA ends is a critical determinant of the pathway used for DNA double-strand break (DSB) repair. Here, we develop an approach involving the hairpin capture of DNA end structures (HCoDES), which elucidates chromosomal DNA end structures at single-nucleotide resolution. HCoDES defines structures of physiologic DSBs generated by the RAG endonuclease, as well as those generated by nucleases widely used for genome editing. Analysis of G1 phase cells deficient in H2AX or 53BP1 reveals DNA ends that are frequently resected to form long single-stranded overhangs that can be repaired by mutagenic pathways. In addition to 3' overhangs, many of these DNA ends unexpectedly form long 5' single-stranded overhangs. The divergence in DNA end structures resolved by HCoDES suggests that H2AX and 53BP1 may have distinct activities in end protection. Thus, the high-resolution end structures obtained by HCoDES identify features of DNA end processing during DSB repair.

AB - The structure of broken DNA ends is a critical determinant of the pathway used for DNA double-strand break (DSB) repair. Here, we develop an approach involving the hairpin capture of DNA end structures (HCoDES), which elucidates chromosomal DNA end structures at single-nucleotide resolution. HCoDES defines structures of physiologic DSBs generated by the RAG endonuclease, as well as those generated by nucleases widely used for genome editing. Analysis of G1 phase cells deficient in H2AX or 53BP1 reveals DNA ends that are frequently resected to form long single-stranded overhangs that can be repaired by mutagenic pathways. In addition to 3' overhangs, many of these DNA ends unexpectedly form long 5' single-stranded overhangs. The divergence in DNA end structures resolved by HCoDES suggests that H2AX and 53BP1 may have distinct activities in end protection. Thus, the high-resolution end structures obtained by HCoDES identify features of DNA end processing during DSB repair.

UR - http://www.scopus.com/inward/record.url?scp=84918808736&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2014.10.024

DO - 10.1016/j.molcel.2014.10.024

M3 - Article

C2 - 25435138

AN - SCOPUS:84918808736

SN - 1097-2765

VL - 56

SP - 808

EP - 818

JO - Molecular cell

JF - Molecular cell

IS - 6

ER -

HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution

Abstract

Access to Document

Other files and links

Fingerprint

Cite this