HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution.
Document Type
Article
Publication Date
12-18-2014
JAX Source
Mol Cell 2014 Dec 18; 56(6):808-18.
Volume
56
Issue
6
First Page
808
Last Page
818
ISSN
1097-4164
PMID
25435138
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. Mol Cell 2014 Dec 18; 56(6):808-18.
Recommended Citation
Dorsett Y,
Zhou Y,
Tubbs A,
Chen B,
Purman C,
Lee B,
George R,
Bredemeyer A,
Zhao J,
Weinstock E,
Weinstock GM,
Han N,
Reyes A,
Oltz E,
Dorsett D,
Misulovin Z,
Payton J,
Sleckman B.
HCoDES Reveals Chromosomal DNA End Structures with Single-Nucleotide Resolution. Mol Cell 2014 Dec 18; 56(6):808-18.