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JWA regulates XRCC1 and functions as a novel base excision repair protein in oxidative-stress-induced DNA single-strand breaks

By Shouyu Wang, Zhenghua Gong, Rui Chen, Yunru Liu, Aiping Li, Gang Li and Jianwei Zhou


JWA was recently demonstrated to be involved in cellular responses to environmental stress including oxidative stress. Although it was found that JWA protected cells from reactive oxygen species-induced DNA damage, upregulated base excision repair (BER) protein XRCC1 and downregulated PARP-1, the molecular mechanism of JWA in regulating the repair of DNA single-strand breaks (SSBs) is still unclear. Our present studies demonstrated that a reduction in JWA protein levels in cells resulted in a decrease of SSB repair capacity and hypersensitivity to DNA-damaging agents such as methyl methanesulfonate and hydrogen peroxide. JWA functioned as a repair protein by multi-interaction with XRCC1. On the one hand, JWA was translocated into the nucleus by the carrier protein XRCC1 and co-localized with XRCC1 foci after oxidative DNA damage. On the other hand, JWA via MAPK signaling pathway regulated nuclear factor E2F1, which further transcriptionally regulated XRCC1. In addition, JWA protected XRCC1 protein from ubiquitination and degradation by proteasome. These findings indicate that JWA may serve as a novel regulator of XRCC1 in the BER protein complex to facilitate the repair of DNA SSBs

Topics: Gene Regulation, Chromatin and Epigenetics
Publisher: Oxford University Press
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Provided by: PubMed Central

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  1. (1992). A Chinese hamster ovary cell mutant (EM-C11) with sensitivity to simple alkylating agents and a very high level of sister chromatid exchanges.
  2. (2008). A dominant role of GTRAP3-18 in neuronal glutathione synthesis.
  3. (1998). A high yield of translocations parallels the high yield of sister chromatid exchanges in the CHO mutant EM9.
  4. (2003). A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage.
  5. (2000). Activation of MEK kinase 1 by the c-Abl protein tyrosine kinase in response to DNA damage.
  6. (2007). Beyond repair foci: subnuclear domains and the cellular response to DNA damage.
  7. (1980). Bovine thymus poly(adenosine diphosphate ribose) polymerase. Physical properties and binding to DNA.
  8. (2008). CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins.
  9. (2008). CHIPping away at base excision repair.
  10. (1999). Defective DNA repair in cells with human T-cell leukemia/bovine leukemia viruses: role of tax gene.
  11. (1997). Detection of DNA lesions induced by chemical mutagens using the single-cell gel electrophoresis (comet) assay. 2. Relationship between DNA migration and alkaline condition.
  12. (2006). Differential recruitment of DNA ligase I and III to DNA repair sites.
  13. (2008). E2F1 regulates the base excision repair gene XRCC1 and promotes DNA repair.
  14. (2006). Early embryonic lethality due to targeted inactivation of DNA ligase III.
  15. (2003). Epidermal growth factor and ionizing radiation up-regulate the DNA repair genes XRCC1 and ERCC1 in DU145 and LNCaP prostate carcinoma through MAPK signaling.
  16. (1998). Excision of C-4’-oxidized deoxyribose lesions from double-stranded DNA by human apurinic/ apyrimidinic endonuclease (Ape1 protein) and DNA polymerase beta.
  17. (2007). Feedback-regulated poly(ADP-ribosyl)ation by PARP-1 is required for rapid response to DNA damage in living cells.
  18. (2006). FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP.
  19. (2007). Identification of JWA as a novel functional gene responsive to environmental oxidative stress induced by benzo[a]-pyrene and hydrogen peroxide. Free Radic.
  20. (2007). Identification of sequences that target BRCA1 to nuclear foci following alkylative DNA damage.
  21. (1986). Incorporated bromodeoxyuridine enhances the sisterchromatid exchange and chromosomal aberration frequencies in an EMS-sensitive Chinese hamster cell line.
  22. (1993). Instability and decay of the primary structure of DNA.
  23. (2007). JWA as a functional molecule to regulate cancer cells migration via MAPK cascades and F-actin cytoskeleton.
  24. (2006). JWA as a novel molecule involved in oxidative stressassociated signal pathway in myelogenous leukemia cells.
  25. (2006). JWA, a novel signaling molecule, involved in
  26. (2006). JWA, a novel signaling molecule, involved in the induction of differentiation of human myeloid leukemia cells.
  27. (2003). Mammalian DNA base excision repair proteins: their interactions and role in repair of oxidative DNA damage.
  28. (2001). Mammalian DNA single-strand break repair: an X-ra(y)ted affair.
  29. (2007). Mammalian single-strand break repair: mechanisms and links with chromatin.
  30. (1990). Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange.
  31. (2003). PKC/Raf/MEK/ERK signaling pathway modulates native-LDL-induced E2F-1 gene expression and endothelial cell proliferation.
  32. (1980). Poly(ADP-ribose) synthesis in vitro programmed by damaged DNA. A comparison of DNA molecules containing different types of strand breaks.
  33. (1981). Poly(ADP-ribose) synthetase, a main acceptor of poly(ADP-ribose) in isolated nuclei.
  34. (1999). Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions.
  35. (2003). Quantitation of intracellular NAD(P)H can monitor an imbalance of DNA single strand break repair in base excision repair deficient cells in real time.
  36. (2008). Ran-binding protein 3 phosphorylation links the Ras and PI3-kinase pathways to nucleocytoplasmic transport.
  37. (2002). Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes.
  38. (2001). Ras induces elevation of E2F-1 mRNA levels.
  39. (1996). Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein.
  40. (2005). Regulation of a novel cell differentiationassociated gene, JWA during oxidative damage in K562 and MCF-7 cells.
  41. (1992). Relationships between DNA damage and the survival of radiosensitive mutant Chinese hamster cell lines exposed to gamma-radiation. Part 1: intrinsic radiosensitivity.
  42. (1995). Requirement for generation of H2O2 for platelet-derived growth factor signal transduction.
  43. (1999). Requirement for the Xrcc1 DNA base excision repair gene during early mouse development.
  44. (2003). Rescue of Xrcc1 knockout mouse embryo lethality by transgenecomplementation.
  45. (1998). Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1.
  46. (2006). Roles of DNA ligase III and XRCC1 in regulating the switch between short patch and long patch BER.
  47. (2001). Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation.
  48. (1996). Signaling events controlling the molecular response to genotoxic stress.
  49. (2008). Single-strand break repair and genetic disease.
  50. (2001). Single-strand interruptions in replicating chromosomes cause double-strand breaks.
  51. (2003). Spatial and temporal cellular responses to single-strand breaks in human cells.
  52. (2003). The cellular response to DNA double-strand breaks: defining the sensors and mediators.
  53. (2005). The E2F transcriptional network: old acquaintances with new faces.
  54. (2000). The hallmarks of cancer.
  55. (2005). The p53 pathway: positive and negative feedback loops.
  56. (2004). The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks.
  57. (2004). XRCC1 co-localizes and physically interacts with PCNA.
  58. (2001). XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions.
  59. (2007). XRCC1 down-regulation in human cells leads to DNA-damaging agent hypersensitivity, elevated sister chromatid exchange, and reduced survival of BRCA2 mutant cells.
  60. (2006). XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage.
  61. (2005). XRCC1 is required for DNA single-strand break repair in human cells.
  62. (1998). XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage.
  63. (2001). XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair.

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