Response of Heterogeneous Ribonuclear Proteins (hnRNP) to Ionising Radiation and Their Involvement in DNA Damage Repair

Overview

Journal Int J Radiat Biol

Specialty Radiology

Date 2009 Jul 7

PMID 19579069

Citations 49

Authors

Benjamin Haley

Tatjana Paunesku

Miroslava Protic

Gayle E Woloschak

Affiliations

Soon will be listed here.

Abstract

Purpose: To determine the relationship between heterogeneous nuclear ribonucleoproteins (hnRNP) and DNA repair, particularly in response to ionising radiation (IR).

Materials And Methods: The literature was examined for papers related to the topics of hnRNP, IR and DNA repair.

Results: HnRNP orchestrate the processing of mRNA to which they are bound in response to IR. HnRNP A18, B1, C1/C2 and K interact with important proteins from DNA Damage Response (DDR) pathways, binding DNA-dependent protein kinase (DNA-PK), the Ku antigen (Ku) and tumour suppressor protein 53 (p53) respectively. Notably, irregularities in the expression of hnRNP A18, B1, K, P2 and L have been linked to cancer and radiosensitivity. Sixteen different hnRNP proteins have been reported to show either mRNA transcript or protein quantity changes following IR. Various protein modifications of hnRNP in response to IR have also been noted: hnRNP A18, C1/C2 and K are phosphorylated; hnRNP C1/C2 is a target of apoptotic proteases; and hnRNP K degradation is controlled by murine double minute ubiquitin ligase (MDM2). Evidence points to a role for hnRNP A1, A18, A2/B1, C1/C2, K and P2 in regulating double-stranded break (DSB) repair pathways by promoting either homologous recombination (HR) or non-homologous end rejoining (NHEJ) repair pathways following IR.

Conclusions: HnRNP proteins play a pivotal role in coordinating repair pathways following exposure to IR, through protein-protein interactions and transcript regulation of key repair and stress response mRNA. In particular, several hnRNP proteins are critical in coordinating the choice of HR or NHEJ to repair DSB caused by IR.

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References

Calvio C, Neubauer G, Mann M, Lamond A . Identification of hnRNP P2 as TLS/FUS using electrospray mass spectrometry. RNA. 1995; 1(7):724-33. PMC: 1369314. View

San Filippo J, Sung P, Klein H . Mechanism of eukaryotic homologous recombination. Annu Rev Biochem. 2008; 77:229-57. DOI: 10.1146/annurev.biochem.77.061306.125255. View

Berggren M, Gallegos A, Gasdaska J, Gasdaska P, Warneke J, Powis G . Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia. Anticancer Res. 1996; 16(6B):3459-66. View

Fanning E, Klimovich V, Nager A . A dynamic model for replication protein A (RPA) function in DNA processing pathways. Nucleic Acids Res. 2006; 34(15):4126-37. PMC: 1616954. DOI: 10.1093/nar/gkl550. View

Edick M, Cheng C, Yang W, Cheok M, Wilkinson M, Pei D . Lymphoid gene expression as a predictor of risk of secondary brain tumors. Genes Chromosomes Cancer. 2004; 42(2):107-16. DOI: 10.1002/gcc.20121. View

Waterhouse N, Kumar S, Song Q, Strike P, Sparrow L, Dreyfuss G . Heteronuclear ribonucleoproteins C1 and C2, components of the spliceosome, are specific targets of interleukin 1beta-converting enzyme-like proteases in apoptosis. J Biol Chem. 1996; 271(46):29335-41. DOI: 10.1074/jbc.271.46.29335. View

Beyer A, Christensen M, Walker B, Lestourgeon W . Identification and characterization of the packaging proteins of core 40S hnRNP particles. Cell. 1977; 11(1):127-38. DOI: 10.1016/0092-8674(77)90323-3. View

Barker S, Weinfeld M, Zheng J, Li L, Murray D . Identification of mammalian proteins cross-linked to DNA by ionizing radiation. J Biol Chem. 2005; 280(40):33826-38. DOI: 10.1074/jbc.M502477200. View

Caceres J, Stamm S, Helfman D, Krainer A . Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors. Science. 1994; 265(5179):1706-9. DOI: 10.1126/science.8085156. View

10.

Bomsztyk K, Van Seuningen I, Suzuki H, Denisenko O, Ostrowski J . Diverse molecular interactions of the hnRNP K protein. FEBS Lett. 1997; 403(2):113-5. DOI: 10.1016/s0014-5793(97)00041-0. View

11.

Sheikh M, Carrier F, Papathanasiou M, Hollander M, Zhan Q, Yu K . Identification of several human homologs of hamster DNA damage-inducible transcripts. Cloning and characterization of a novel UV-inducible cDNA that codes for a putative RNA-binding protein. J Biol Chem. 1997; 272(42):26720-6. DOI: 10.1074/jbc.272.42.26720. View

12.

Yang C, Carrier F . The UV-inducible RNA-binding protein A18 (A18 hnRNP) plays a protective role in the genotoxic stress response. J Biol Chem. 2001; 276(50):47277-84. DOI: 10.1074/jbc.M105396200. View

13.

van Der Houven Van Oordt W, Diaz-Meco M, Lozano J, Krainer A, Moscat J, Caceres J . The MKK(3/6)-p38-signaling cascade alters the subcellular distribution of hnRNP A1 and modulates alternative splicing regulation. J Cell Biol. 2000; 149(2):307-16. PMC: 2175157. DOI: 10.1083/jcb.149.2.307. View

14.

Sonoda E, Hochegger H, Saberi A, Taniguchi Y, Takeda S . Differential usage of non-homologous end-joining and homologous recombination in double strand break repair. DNA Repair (Amst). 2006; 5(9-10):1021-9. DOI: 10.1016/j.dnarep.2006.05.022. View

15.

Yim E, Lee K, Kim C, Park J . Analysis of differential protein expression by cisplatin treatment in cervical carcinoma cells. Int J Gynecol Cancer. 2006; 16(2):690-7. DOI: 10.1111/j.1525-1438.2006.00586.x. View

16.

Gamble S, Dunn M, WHEELER C, Joiner M, Arrand J . Expression of proteins coincident with inducible radioprotection in human lung epithelial cells. Cancer Res. 2000; 60(8):2146-51. View

17.

Jen K, Cheung V . Transcriptional response of lymphoblastoid cells to ionizing radiation. Genome Res. 2003; 13(9):2092-100. PMC: 403696. DOI: 10.1101/gr.1240103. View

18.

Klimek-Tomczak K, Wyrwicz L, Jain S, Bomsztyk K, Ostrowski J . Characterization of hnRNP K protein-RNA interactions. J Mol Biol. 2004; 342(4):1131-41. DOI: 10.1016/j.jmb.2004.07.099. View

19.

Pinol-Roma S, Dreyfuss G . Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature. 1992; 355(6362):730-2. DOI: 10.1038/355730a0. View

20.

Kim L, Kimmel A . GSK3, a master switch regulating cell-fate specification and tumorigenesis. Curr Opin Genet Dev. 2000; 10(5):508-14. DOI: 10.1016/s0959-437x(00)00120-9. View