Damage-induced localized hypermutability

Lauranell H Burch; Yong Yang; Joan F Sterling; Steven A Roberts; Frank G Chao; Hong Xu; Leilei Zhang; Jesse Walsh; Michael A Resnick; Piotr A Mieczkowski; Dmitry A Gordenin

doi:10.4161/cc.10.7.15319

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Damage-induced localized hypermutability

Journal article

Open access

Peer reviewed

Damage-induced localized hypermutability

Lauranell H Burch, Yong Yang, Joan F Sterling, Steven A Roberts, Frank G Chao, Hong Xu, Leilei Zhang, Jesse Walsh, Michael A Resnick, Piotr A Mieczkowski, …

Cell cycle (Georgetown, Tex.), Vol.10(7), pp.1073-1085

04/01/2011

DOI: https://doi.org/10.4161/cc.10.7.15319

Handle:

https://hdl.handle.net/2376/116078

PMCID: PMC3100884

PMID: 21406975

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https://doi.org/10.4161/cc.10.7.15319View

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Abstract

DNA damage and repair

evolution

hypermutability

double-strand breaks

single-strand DNA

Genome instability continuously presents perils of cancer, genetic disease and death of a cell or an organism. At the same time, it provides for genome plasticity that is essential for development and evolution. We address here the genome instability confined to a small fraction of DNA adjacent to free DNA ends at uncapped telomeres and double-strand breaks. We found that budding yeast cells can tolerate nearly 20 kilobase regions of subtelomeric single-strand DNA that contain multiple UV-damaged nucleotides. During restoration to the double-strand state, multiple mutations are generated by error-prone translesion synthesis. Genome-wide sequencing demonstrated that multiple regions of damage-induced localized hypermutability can be tolerated, which leads to the simultaneous appearance of multiple mutation clusters in the genomes of UV-irradiated cells. High multiplicity and density of mutations suggest that this novel form of genome instability may play significant roles in generating new alleles for evolutionary selection as well as in the incidence of cancer and genetic disease.

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Title: Damage-induced localized hypermutability
Creators: Lauranell H Burch - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Yong Yang - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Joan F Sterling - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Steven A Roberts - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Frank G Chao - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Hong Xu - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Leilei Zhang - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Jesse Walsh - Department of Genetics; School of Medicine; University of North Carolina at Chapel Hill; Chapel Hill, NC USA
Michael A Resnick - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Piotr A Mieczkowski - Department of Genetics; School of Medicine; University of North Carolina at Chapel Hill; Chapel Hill, NC USA
Dmitry A Gordenin - Laboratory of Molecular Genetics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA
Publication Details: Cell cycle (Georgetown, Tex.), Vol.10(7), pp.1073-1085
Academic Unit: Plant Pathology, Department of; Molecular Biosciences, School of
Publisher: Landes Bioscience
Identifiers: 99900548075701842
Language: English
Resource Type: Journal article