Genome-wide surveillance of transcription errors in response to genotoxic stress

被引：23

作者：

Fritsch, C. ^{[1
]}

Gout, J-F ^{[2
,3
]}

Haroon, S. ^{[4
]}

Towheed, A. ^{[5
]}

Chung, C. ^{[6
]}

LaGosh, J. ^{[6
]}

McGann, E. ^{[6
]}

Zhang, X. ^{[7
]}

Song, Y. ^{[8
,9
]}

Simpson, S. ^{[10
]}

Danthi, P. S. ^{[6
]}

Benayoun, B. A. ^{[6
]}

Wallace, D. ^{[9
,11
]}

Thomas, K. ^{[10
]}

Lynch, M. ^{[2
]}

Vermulst, M. ^{[6
,11
]}

机构：

[1] Univ Penn, Dept Cellular & Mol Biol, Philadelphia, PA 19104 USA

[2] Arizona State Univ, Biodesign Ctr Mech Evolut, Sch Life Sci, Tempe, AZ 85287 USA

[3] Mississippi State Univ, Dept Biol Sci, Mississippi State, MS 39762 USA

[4] Childrens Hosp Philadelphia, Dept Human Genet, Philadelphia, PA 19104 USA

[5] Touro Coll Osteopath Med, Middletown, NY 10940 USA

[6] Univ Southern Calif, Sch Gerontol, Los Angeles, CA 90089 USA

[7] Bioinforx Inc, Madison, WI 53719 USA

[8] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[9] Univ Penn, Raymond G Perelman Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA

[10] Univ New Hampshire, Dept Mol Cellular & Biomed Sci, Durham, NH 03824 USA

[11] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2021年 / 118卷 / 01期

关键词：

transcription error; mutagenesis; genotoxic stress; DNA damage; RNA-POLYMERASE-II; DNA-REPAIR; N-METHYL-N'-NITRO-N-NITROSOGUANIDINE MUTAGENESIS; PHENOTYPIC CHANGE; DAMAGE; GENE; ALZHEIMERS; SEQUENCE; MUTATION; NUCLEAR;

D O I：

10.1073/pnas.2004077118

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.

引用

页数：7

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