Gene Symbol: Rnf8
Description: ring finger protein 8
Alias: 3830404E21Rik, AIP37, laXp180, E3 ubiquitin-protein ligase RNF8, ActA binding protein 2, RING-type E3 ubiquitin transferase RNF8, actA-interacting protein 37
Species: mouse
Products:     Rnf8

Top Publications

  1. Sin H, Barski A, Zhang F, Kartashov A, Nussenzweig A, Chen J, et al. RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in post-meiotic spermatids. Genes Dev. 2012;26:2737-48 pubmed publisher
    ..We show that RNF8-dependent ubiquitination of histone H2A during meiosis establishes active epigenetic modifications, including ..
  2. Wu J, Chen Y, Lu L, Wu Y, Paulsen M, Ljungman M, et al. Chfr and RNF8 synergistically regulate ATM activation. Nat Struct Mol Biol. 2011;18:761-8 pubmed publisher
    ..of the DNA damage-induced ubiquitination pathway, we analyzed the impact of the loss of two E3 ubiquitin ligases, RNF8 and Chfr...
  3. Wu J, Huen M, Lu L, Ye L, Dou Y, Ljungman M, et al. Histone ubiquitination associates with BRCA1-dependent DNA damage response. Mol Cell Biol. 2009;29:849-60 pubmed publisher
    ..Moreover, we have found that RNF8 (ring finger protein 8), an E3 ubiquitin ligase, regulates ubiquitination of both histones H2A and H2B...
  4. Rai R, Li J, Zheng H, Lok G, Deng Y, Huen M, et al. The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection. Nat Struct Mol Biol. 2011;18:1400-7 pubmed publisher
    ..Here we show that in Mus musculus, the E3 ubiquitin ligase Rnf8 localizes to uncapped telomeres and promotes the accumulation of DNA damage proteins 53Bp1 and ?-H2ax...
  5. Santos M, Huen M, Jankovic M, Chen H, López Contreras A, Klein I, et al. Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8. J Exp Med. 2010;207:973-81 pubmed publisher
    ..interaction with DNA double-strand breaks (DSBs), one by binding to methylated histones and the other via an RNF8 E3 ligase-dependent ubiquitylation pathway...
  6. Feng L, Chen J. The E3 ligase RNF8 regulates KU80 removal and NHEJ repair. Nat Struct Mol Biol. 2012;19:201-6 pubmed publisher
    ..The E3 ubiquitin ligase RING finger protein 8 (RNF8) triggers the initial ubiquitination at double-strand DNA breaks, whereas sustained ubiquitination requires the ..
  7. Lu L, Wu J, Ye L, Gavrilina G, Saunders T, Yu X. RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis. Dev Cell. 2010;18:371-84 pubmed publisher
    ..In this study, we investigate the role of the ubiquitin ligase RNF8 during spermatogenesis and find that RNF8-deficient mice are proficient in meiotic sex chromosome inactivation (..
  8. Li L, Halaby M, Hakem A, Cardoso R, El Ghamrasni S, Harding S, et al. Rnf8 deficiency impairs class switch recombination, spermatogenesis, and genomic integrity and predisposes for cancer. J Exp Med. 2010;207:983-97 pubmed publisher
    ..Recent studies reported that the E3 ligase RNF8 plays important roles in propagating DNA DSB signals and thereby facilitating the recruitment of various DNA damage ..
  9. Ichijima Y, Ichijima M, Lou Z, Nussenzweig A, Camerini Otero R, Chen J, et al. MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells. Genes Dev. 2011;25:959-71 pubmed publisher
    ..These results establish that the DDR pathway centered on MDC1 triggers epigenetic silencing of sex chromosomes in germ cells...

More Information


  1. Huen M, Huang J, Yuan J, Yamamoto M, Akira S, Ashley C, et al. Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol Cell Biol. 2008;28:6104-12 pubmed publisher
    ..Recent studies have elucidated that UBC13, in concert with the E3 ubiquitin ligase RNF8, propagates the DNA damage signal via a ubiquitylation-dependent signaling pathway...
  2. Ramachandran S, Chahwan R, Nepal R, Frieder D, Panier S, Roa S, et al. The RNF8/RNF168 ubiquitin ligase cascade facilitates class switch recombination. Proc Natl Acad Sci U S A. 2010;107:809-14 pubmed publisher
    ..The DNA damage response E3 ubiquitin ligases RNF8 and RNF168 were recently shown to facilitate recruitment of 53BP1 to sites of DNA damage...
  3. Pfeuffer T, Goebel W, Laubinger J, Bachmann M, Kuhn M. LaXp180, a mammalian ActA-binding protein, identified with the yeast two-hybrid system, co-localizes with intracellular Listeria monocytogenes. Cell Microbiol. 2000;2:101-14 pubmed
    ..monocytogenes EGD as bait. Three different AIPs were identified, one of which was identical to the human protein LaXp180 (also called CC1)...
  4. Lee H, Li C, Ruan D, Powers S, Thompson P, Frohman M, et al. The DNA Damage Transducer RNF8 Facilitates Cancer Chemoresistance and Progression through Twist Activation. Mol Cell. 2016;63:1021-33 pubmed publisher
    ..Through an E3 ligase screen and biochemical studies, we unexpectedly identified that RNF8 functions as a direct Twist activator by triggering K63-linked ubiquitination of Twist...
  5. Peuscher M, Jacobs J. DNA-damage response and repair activities at uncapped telomeres depend on RNF8. Nat Cell Biol. 2011;13:1139-45 pubmed publisher
    ..Here we show that uncapped telomeres accumulate ubiquitylated histone H2A in a manner dependent on the E3 ligase RNF8. The ability of RNF8 to ubiquitylate telomeric chromatin is associated with its capacity to facilitate accumulation ..
  6. Alavattam K, Kato Y, Sin H, Maezawa S, Kowalski I, Zhang F, et al. Elucidation of the Fanconi Anemia Protein Network in Meiosis and Its Function in the Regulation of Histone Modifications. Cell Rep. 2016;17:1141-1157 pubmed publisher
    ..FA core factors FANCA, FANCB, and FANCC are essential for FANCD2 foci formation, whereas BRCA1 (FANCS), MDC1, and RNF8 are required for BRCA2 (FANCD1) and SLX4 (FANCP) accumulation on the sex chromosomes during meiosis...
  7. Luijsterburg M, Acs K, Ackermann L, Wiegant W, Bekker Jensen S, Larsen D, et al. A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure. EMBO J. 2012;31:2511-27 pubmed publisher
    The ubiquitin ligases RNF8 and RNF168 orchestrate DNA damage signalling through the ubiquitylation of histone H2A and the recruitment of downstream repair factors...
  8. Hodge C, Ismail I, Edwards R, Hura G, Xiao A, Tainer J, et al. RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. J Biol Chem. 2016;291:9396-410 pubmed publisher
    DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB ..
  9. Kato Y, Alavattam K, Sin H, Meetei A, Pang Q, Andreassen P, et al. FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis. Hum Mol Genet. 2015;24:5234-49 pubmed publisher
    ..Taken together, these results indicate that FANCB functions at critical stages of germ cell development and reveal a novel function of the FA pathway in the regulation of H3K9 methylation in the germline. ..
  10. Hasegawa K, Sin H, Maezawa S, Broering T, Kartashov A, Alavattam K, et al. SCML2 establishes the male germline epigenome through regulation of histone H2A ubiquitination. Dev Cell. 2015;32:574-88 pubmed publisher
    ..Our results reveal divergent mechanisms involving a shared regulator by which the male germline epigenome is distinguished from that of the soma and progenitor cells. ..
  11. Lilley C, Chaurushiya M, Boutell C, Landry S, Suh J, Panier S, et al. A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. EMBO J. 2010;29:943-55 pubmed publisher
    ..We identify RNF8 and RNF168, cellular histone ubiquitin ligases responsible for anchoring repair factors at sites of damage, as new ..
  12. Liu C, Wu J, Paudyal S, You Z, Yu X. CHFR is important for the first wave of ubiquitination at DNA damage sites. Nucleic Acids Res. 2013;41:1698-710 pubmed publisher
    ..Thus, these results demonstrate that CHFR is an important E3 ligase in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. ..
  13. Ouyang S, Song Y, Tian Y, Chen Y, Yu X, Wang D. RNF8 deficiency results in neurodegeneration in mice. Neurobiol Aging. 2015;36:2850-2860 pubmed publisher
    ..The ubiquitin ligase RNF8 plays an important role in DNA double-strand break repair via histone ubiquitination...
  14. Gou L, Kang J, Dai P, Wang X, Li F, Zhao S, et al. Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis. Cell. 2017;169:1090-1104.e13 pubmed publisher
    ..Mechanistically, we show that MIWI binds the histone ubiquitin ligase RNF8 in a Piwi-interacting RNA (piRNA)-independent manner, and MIWI stabilization sequesters RNF8 in the cytoplasm of ..
  15. Minter Dykhouse K, Ward I, Huen M, Chen J, Lou Z. Distinct versus overlapping functions of MDC1 and 53BP1 in DNA damage response and tumorigenesis. J Cell Biol. 2008;181:727-35 pubmed publisher
    ..We additionally show that MDC1 regulates 53BP1 foci formation and phosphorylation in response to DNA damage. These results suggest that MDC1 functions as an upstream regulator of 53BP1 in the DDR pathway and in tumor suppression. ..
  16. Yuan J, Chen J. FIGNL1-containing protein complex is required for efficient homologous recombination repair. Proc Natl Acad Sci U S A. 2013;110:10640-5 pubmed publisher
    ..Collectively, our study uncovers a protein complex, which consists of FIGNL1 and KIAA0146/SPIDR, in DNA repair and provides potential directions for cancer diagnosis and therapy. ..
  17. Zhang S, Zhou Y, Sarkeshik A, Yates J, Thomson T, Zhang Z, et al. Identification of RNF8 as a ubiquitin ligase involved in targeting the p12 subunit of DNA polymerase ? for degradation in response to DNA damage. J Biol Chem. 2013;288:2941-50 pubmed publisher
    ..Proteomic analysis revealed that RNF8, a RING finger ubiquitin ligase that plays an important role in the DNA damage response, was the only ubiquitin ..
  18. Wu J, Prindle M, Dressler G, Yu X. PTIP regulates 53BP1 and SMC1 at the DNA damage sites. J Biol Chem. 2009;284:18078-84 pubmed publisher
    ..Here, we show that RNF8 controls DNA damage-induced nuclear foci formation of PTIP, which in turn regulates 53BP1 localization to the DNA ..
  19. Gong Z, Cho Y, Kim J, Ge K, Chen J. Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage. J Biol Chem. 2009;284:7284-93 pubmed publisher
    ..MDC1.RNF8, which in turn facilitates sustained localization of PA1 (PTIP-associated protein 1) to sites of DNA break...
  20. Halaby M, Hakem A, Li L, El Ghamrasni S, Venkatesan S, Hande P, et al. Synergistic interaction of Rnf8 and p53 in the protection against genomic instability and tumorigenesis. PLoS Genet. 2013;9:e1003259 pubmed publisher
    b>Rnf8 is an E3 ubiquitin ligase that plays a key role in the DNA damage response as well as in the maintenance of telomeres and chromatin remodeling...
  21. Wang J, Gong Z, Chen J. MDC1 collaborates with TopBP1 in DNA replication checkpoint control. J Cell Biol. 2011;193:267-73 pubmed publisher
    ..Collectively, our data suggest that MDC1 facilitates several important steps in both cellular DNA damage response and the DNA replication checkpoint. ..
  22. Valnegri P, Huang J, Yamada T, Yang Y, Mejia L, Cho H, et al. RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain. Nat Commun. 2017;8:1271 pubmed publisher
    ..Here, we report that in vivo knockdown or conditional knockout of the autism-linked ubiquitin ligase RNF8 or associated ubiquitin-conjugating enzyme UBC13 in rodent cerebellar granule neurons robustly increases the number ..