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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.
| Acronyms | ||
| 14-3-3σ | = | stratifin |
| ATM | = | Ataxia Telangiectasia Mutated kinase |
| ATR | = | Ataxia Telangiectasia Rad3 related kinase |
| CHiP | = | Chromatin immunoprecipitation |
| CIRP | = | cold-inducible RNA-binding protein |
| Cs-137 | = | cesium-137 |
| Co-60 | = | cobalt-60 |
| DDR | = | DNA damage response |
| DSB | = | double-strand breaks |
| DNA-PK | = | DNA-dependent protein kinase |
| Gy | = | gray |
| GSK3β | = | glycogen synthase kinase 3 beta |
| HDM2 | = | human homologue of murine double minute |
| hnRNP | = | Heterogeneous ribonucleoprotein |
| HR | = | homologous recombination |
| IR | = | ionising radiation |
| Ku | = | Ku antigen, 70kDa and/or 80 kDa subunit |
| MDM2 | = | murine double minute, a p53 ubiquin ligase (mouse) |
| Mre11 | = | meiotic recombination 11 homologue |
| Nbs1 | = | Nirbrin |
| NGF | = | Nerve Growth Factor |
| NHEJ | = | non-homologous end joining |
| p21 | = | Cyclin-dependent kinase inhibitor 1A |
| p53 | = | tumour protein 53 |
| PIKK | = | phosphatidylinositol 3-kinase-like kinase |
| Rad50 | = | Rad50 homologue |
| RGG | = | arginine-glycine-glycine |
| RNP | = | ribonuclear proteins |
| RPA | = | Replication protein A |
| siRNA | = | short interfering RNA |
| TERT | = | Telomerase Reverse Transcriptase |
| TLS/FUS | = | Translocated/Fusion |
| = | hnRNP P2 | |
| UV | = | ultraviolet |
| UV-B | = | medium wavelength ultraviolet |
| UV-C | = | shortwave ultraviolet |
| UP1 | = | Unwinding Protein 1 |
| XRCC4 | = | X-ray repair in Chinese hamster cells 4 protein |
| Acronyms | ||
| 14-3-3σ | = | stratifin |
| ATM | = | Ataxia Telangiectasia Mutated kinase |
| ATR | = | Ataxia Telangiectasia Rad3 related kinase |
| CHiP | = | Chromatin immunoprecipitation |
| CIRP | = | cold-inducible RNA-binding protein |
| Cs-137 | = | cesium-137 |
| Co-60 | = | cobalt-60 |
| DDR | = | DNA damage response |
| DSB | = | double-strand breaks |
| DNA-PK | = | DNA-dependent protein kinase |
| Gy | = | gray |
| GSK3β | = | glycogen synthase kinase 3 beta |
| HDM2 | = | human homologue of murine double minute |
| hnRNP | = | Heterogeneous ribonucleoprotein |
| HR | = | homologous recombination |
| IR | = | ionising radiation |
| Ku | = | Ku antigen, 70kDa and/or 80 kDa subunit |
| MDM2 | = | murine double minute, a p53 ubiquin ligase (mouse) |
| Mre11 | = | meiotic recombination 11 homologue |
| Nbs1 | = | Nirbrin |
| NGF | = | Nerve Growth Factor |
| NHEJ | = | non-homologous end joining |
| p21 | = | Cyclin-dependent kinase inhibitor 1A |
| p53 | = | tumour protein 53 |
| PIKK | = | phosphatidylinositol 3-kinase-like kinase |
| Rad50 | = | Rad50 homologue |
| RGG | = | arginine-glycine-glycine |
| RNP | = | ribonuclear proteins |
| RPA | = | Replication protein A |
| siRNA | = | short interfering RNA |
| TERT | = | Telomerase Reverse Transcriptase |
| TLS/FUS | = | Translocated/Fusion |
| = | hnRNP P2 | |
| UV | = | ultraviolet |
| UV-B | = | medium wavelength ultraviolet |
| UV-C | = | shortwave ultraviolet |
| UP1 | = | Unwinding Protein 1 |
| XRCC4 | = | X-ray repair in Chinese hamster cells 4 protein |