Novel Approach Reveals Genomic Landscapes of Single-strand DNA Breaks with Nucleotide Resolution in Human Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Dec 22

PMID 31862872

Citations 27

Authors

Huifen Cao

Lorena Salazar-Garcia

Fan Gao

Thor Wahlestedt

Chun-Lin Wu

Xueer Han

Ye Cai

Dongyang Xu

Fang Wang

Lu Tang

Natalie Ricciardi

DingDing Cai

Huifang Wang

Mario P S Chin

James A Timmons

Claes Wahlestedt

Philipp Kapranov

Affiliations

Soon will be listed here.

Abstract

Single-strand breaks (SSBs) represent the major form of DNA damage, yet techniques to map these lesions genome-wide with nucleotide-level precision are limited. Here, we present a method, termed SSiNGLe, and demonstrate its utility to explore the distribution and dynamic changes in genome-wide SSBs in response to different biological and environmental stimuli. We validate SSiNGLe using two very distinct sequencing techniques and apply it to derive global profiles of SSBs in different biological states. Strikingly, we show that patterns of SSBs in the genome are non-random, specific to different biological states, enriched in regulatory elements, exons, introns, specific types of repeats and exhibit differential preference for the template strand between exons and introns. Furthermore, we show that breaks likely contribute to naturally occurring sequence variants. Finally, we demonstrate strong links between SSB patterns and age. Overall, SSiNGLe provides access to unexplored realms of cellular biology, not obtainable with current approaches.

Citing Articles

Methods and applications of genome-wide profiling of DNA damage and rare mutations.

Pfeifer G, Jin S Nat Rev Genet. 2024; 25(12):846-863.

PMID: 38918545 PMC: 11563917. DOI: 10.1038/s41576-024-00748-4.

Impact of double-strand breaks induced by uv radiation on neuroinflammation and neurodegenerative disorders.

Vijayakumar S, Yesudhason B, Anandharaj J, Sathyaraj W, Selvan Christyraj J Mol Biol Rep. 2024; 51(1):725.

PMID: 38851636 DOI: 10.1007/s11033-024-09693-1.

Common occurrence of hotspots of single strand DNA breaks at transcriptional start sites.

Cao H, Zhang Y, Song T, Xia L, Cai Y, Kapranov P BMC Genomics. 2024; 25(1):368.

PMID: 38622509 PMC: 11017599. DOI: 10.1186/s12864-024-10284-4.

Genome-wide profiles of DNA damage represent highly accurate predictors of mammalian age.

Cao H, Deng B, Song T, Lian J, Xia L, Chu X Aging Cell. 2024; 23(5):e14122.

PMID: 38391092 PMC: 11113270. DOI: 10.1111/acel.14122.

SSBlazer: a genome-wide nucleotide-resolution model for predicting single-strand break sites.

Xu S, Wei J, Sun S, Zhang J, Chan T, Li Y Genome Biol. 2024; 25(1):46.

PMID: 38347618 PMC: 10863285. DOI: 10.1186/s13059-024-03179-w.

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