Cell Transcriptional State Alters Genomic Patterns of DNA Double-strand Break Repair in Human Astrocytes

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Dec 18

PMID 25517576

Citations 9

Authors

Raymund L Yong

Chunzhang Yang

Jie Lu

Huaien Wang

Cody D Schlaff

Anita Tandle

Christian A Graves

Abdel G Elkahloun

Xiaoyuan Chen

Zhengping Zhuang

Russell R Lonser

Affiliations

Soon will be listed here.

Abstract

The misrepair of DNA double-strand breaks in close spatial proximity within the nucleus can result in chromosomal rearrangements that are important in the pathogenesis of haematopoietic and solid malignancies. It is unknown why certain epigenetic states, such as those found in stem or progenitor cells, appear to facilitate neoplastic transformation. Here we show that altering the transcriptional state of human astrocytes alters patterns of DNA damage repair from ionizing radiation at a gene locus-specific and genome-wide level. Astrocytes induced into a reactive state exhibit increased DNA repair, compared with non-reactive cells, in actively transcribed chromatin after irradiation. In mapping these repair sites, we identify misrepair events and repair hotspots that are unique to each state. The precise characterization of genomic regions susceptible to mutation in specific transcriptional states provides new opportunities for addressing clonal evolution in solid cancers, in particular those where double-strand break induction is a cornerstone of clinical intervention.

Citing Articles

Unraveling astrocyte behavior in the space brain: Radiation response of primary astrocytes.

Roggan M, Kronenberg J, Wollert E, Hoffmann S, Nisar H, Konda B Front Public Health. 2023; 11:1063250.

PMID: 37089489 PMC: 10116417. DOI: 10.3389/fpubh.2023.1063250.

Radiation resistance of normal human astrocytes: the role of non-homologous end joining DNA repair activity.

Bylicky M, Mueller G, Day R J Radiat Res. 2018; 60(1):37-50.

PMID: 30423138 PMC: 6373697. DOI: 10.1093/jrr/rry084.

Mechanisms of Endogenous Neuroprotective Effects of Astrocytes in Brain Injury.

Bylicky M, Mueller G, Day R Oxid Med Cell Longev. 2018; 2018:6501031.

PMID: 29805731 PMC: 5901819. DOI: 10.1155/2018/6501031.

Treatment-associated DNA-binding domain missense mutations in the pathogenesis of secondary gliosarcoma.

Pain M, Wang H, Lee E, Strahl M, Hamou W, Sebra R Oncotarget. 2018; 9(2):2603-2621.

PMID: 29416795 PMC: 5788663. DOI: 10.18632/oncotarget.23517.

Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery.

Li P, Stetler R, Leak R, Shi Y, Li Y, Yu W Neuropharmacology. 2017; 134(Pt B):208-217.

PMID: 29128308 PMC: 5940593. DOI: 10.1016/j.neuropharm.2017.11.011.

References

Keogh M, Kim J, Downey M, Fillingham J, Chowdhury D, Harrison J . A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2005; 439(7075):497-501. DOI: 10.1038/nature04384. View

Rabbitts T . Commonality but diversity in cancer gene fusions. Cell. 2009; 137(3):391-5. DOI: 10.1016/j.cell.2009.04.034. View

Buffo A, Rite I, Tripathi P, Lepier A, Colak D, Horn A . Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain. Proc Natl Acad Sci U S A. 2008; 105(9):3581-6. PMC: 2265175. DOI: 10.1073/pnas.0709002105. View

Friedman D, Whitton J, Leisenring W, Mertens A, Hammond S, Stovall M . Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2010; 102(14):1083-95. PMC: 2907408. DOI: 10.1093/jnci/djq238. View

Yang P, Kollmeyer T, Buckner K, Bamlet W, Ballman K, Jenkins R . Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer. 2005; 103(11):2363-72. DOI: 10.1002/cncr.21028. View

Shibuya S, Miyamoto O, Auer R, Itano T, Mori S, Norimatsu H . Embryonic intermediate filament, nestin, expression following traumatic spinal cord injury in adult rats. Neuroscience. 2002; 114(4):905-16. DOI: 10.1016/s0306-4522(02)00323-8. View

Bonner W, Redon C, Dickey J, Nakamura A, Sedelnikova O, Solier S . GammaH2AX and cancer. Nat Rev Cancer. 2008; 8(12):957-67. PMC: 3094856. DOI: 10.1038/nrc2523. View

Yu T, Cao G, Feng L . Low temperature induced de-differentiation of astrocytes. J Cell Biochem. 2006; 99(4):1096-107. DOI: 10.1002/jcb.20979. View

Mitelman F, Johansson B, Mertens F . The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer. 2007; 7(4):233-45. DOI: 10.1038/nrc2091. View

10.

Hakim O, Resch W, Yamane A, Klein I, Kieffer-Kwon K, Jankovic M . DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. Nature. 2012; 484(7392):69-74. PMC: 3459314. DOI: 10.1038/nature10909. View

11.

Forrester H, Radford I . Detection and sequencing of ionizing radiation-induced DNA rearrangements using the inverse polymerase chain reaction. Int J Radiat Biol. 1998; 74(1):1-15. DOI: 10.1080/095530098141672. View

12.

Lu X, de la Pena L, Barker C, Camphausen K, Tofilon P . Radiation-induced changes in gene expression involve recruitment of existing messenger RNAs to and away from polysomes. Cancer Res. 2006; 66(2):1052-61. DOI: 10.1158/0008-5472.CAN-05-3459. View

13.

Cappell K, Larson B, Sciaky N, Whitehurst A . Symplekin specifies mitotic fidelity by supporting microtubule dynamics. Mol Cell Biol. 2010; 30(21):5135-44. PMC: 2953045. DOI: 10.1128/MCB.00758-10. View

14.

Dong H, Luo L, Hong S, Siu H, Xiao Y, Jin L . Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma. BMC Syst Biol. 2010; 4:163. PMC: 3002314. DOI: 10.1186/1752-0509-4-163. View

15.

Buchert M, Papin M, Bonnans C, Darido C, Raye W, Garambois V . Symplekin promotes tumorigenicity by up-regulating claudin-2 expression. Proc Natl Acad Sci U S A. 2010; 107(6):2628-33. PMC: 2823888. DOI: 10.1073/pnas.0903747107. View

16.

Peyre H, Coffigny H, Reillaudou M, Beaumatin J, Morin M, Luccioni C . Transformation by radiation of rat foetal glial cells. Int J Radiat Biol. 2000; 76(1):87-94. DOI: 10.1080/095530000139041. View

17.

Puerto S, Ramirez M, Marcos R, Creus A, Surralles J . Radiation-induced chromosome aberrations in human euchromatic (17cen-p53) and heterochromatic (1cen-1q12) regions. Mutagenesis. 2001; 16(4):291-6. DOI: 10.1093/mutage/16.4.291. View

18.

Dufour C, Cadusseau J, Varlet P, Surena A, de Faria G, Dias-Morais A . Astrocytes reverted to a neural progenitor-like state with transforming growth factor alpha are sensitized to cancerous transformation. Stem Cells. 2009; 27(10):2373-82. PMC: 3245240. DOI: 10.1002/stem.155. View

19.

Cowell I, Sunter N, Singh P, Austin C, Durkacz B, Tilby M . gammaH2AX foci form preferentially in euchromatin after ionising-radiation. PLoS One. 2007; 2(10):e1057. PMC: 2020439. DOI: 10.1371/journal.pone.0001057. View

20.

Neglia J, Robison L, Stovall M, Liu Y, Packer R, Hammond S . New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006; 98(21):1528-37. DOI: 10.1093/jnci/djj411. View