The EMBO Journal Vol.16 No.22 pp.6874–6885, 1997 Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions Shengfang Jin and David T.Weaver1 Division of

suggest that the binding of the Ku80 and Ku70 proteins to DNA plays an important role in the joining of both signal and coding ends. On the other hand, the scid

DNA interaction assay. 2009-03-30 2016-12-20 First, either Ku70 or Ku80 functions outside the Ku heterodimer such that deletion of one is not identical to deletion of the other. Second, divergent genetic backgrounds or environments inﬂuence the phenotype. To distinguish between these possi-bilities, the Ku70 and Ku80 mutations were crossed together to generate Ku70, Ku80, and double Ku70 and Ku80 heterodimers function as regulatory subunits of the DNA-dependent protein kinase and play a very important role in the repairing of DNA double-strand breaks. 2013-07-01 There was no correlation between the transcript levels of Ku80 and LUC luminescence derived from T‐DNA stable transformation in KD‐OsKu80 rice calli (Figs 1b, 2d,e). It has been shown that the Ku70/80 protein functions as a heterodimer to repair DSBs, with the two constituents stabilizing each other (Smider et al., 1994). 2016-07-08 DNA-PKcs functions both within and outside of the damage response to effectively design therapeutic strategies.

Ku70 and ku80 function

Biochemical analyses of the Ku70-Ku80 het-erodimer protein demonstrated that it bound in a sequence-nonspecific fashion to virtually all double-stranded DNA ends including 5 -or3-protruding ends, blunt ends (32), and duplex DNA ending in stem–loop structures (33). The DNA binding activity of the Ku70-Ku80 heterodimer is thought to function by LSE is an autoimmune disease, whereby the immune system mistakenly attacks healthy tissue, resulting in red rash, as a response of inflammation. Both the Ku70 and Ku80 subunits were subcloned (Reeves and Sthoeger 1989; Mimori et al. 1990), but the breakthrough occurred with the discovery Ku70 and Ku80 heterodimers function as regulatory subunits of the DNA-dependent protein kinase and play a very important role in the repairing of DNA double-strand breaks. Although Ku70 is The Ku protein, a heterodimer consisting of Ku70 and Ku80 subunits, is a multifunctional complex playing critical roles in important cellular processes such as non-homologous end joining (NHEJ), V (D)J recombination, apoptosis, telomere maintenance and DNA replication (1). The propensity for Ku70 to associate with Ku80 and to bind DNA correlates with the ability to activate DNA-PK, although two mutants showed that the roles of Ku70 in DNA-PK activation and IR repair Initially, broken DNA ends are recognized and processed, a mechanism initiated by the Ku70/80 heterodimer, which recruits DNA-dependent protein kinase and repair factor Artemis for end modification. Next, the broken DNA is ligated through a complex consisting of DNA ligase IV (Lig4), XRCC4, and Cernunnos/XLF (1).

Function Together, Ku70 and Ku80 make up the Ku heterodimer , which binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair . It is also required for V(D)J recombination , which utilizes the NHEJ pathway to promote antigen diversity in the mammalian immune system .

We show that the Ku70 NLS has a higher affinity for Impα than the Ku80 NLS, consistent with more extensive interactions in its N-terminal region. 1997-07-01 ing of Ku70 and Ku80, which recognizes DSBs and recruits addi - tional pathway components to process and repair the Fbxo28 and Kdm2b.

Ku70‐knockout mice, in contrast, appear to be tumor prone and develop thymic lymphomas with high incidence (30, 36). Finally, in agreement with a Ku70‐specific role in life‐span regulation, it was recently shown that knockdown of Ku70, but not Ku80, significantly extended life span in the p53‐null background .

Required for mating-type switching (By similarity). 2011-01-12 The proteins Ku70 (69.8 kDa) and Ku80 (82.7 kDa) form a heterodimeric complex that is an essential component of the nonhomologous end joining DNA double-strand break repair pathway in mammalian cells. Interaction of Ku with DNA is central for the functions of Ku. 2001-03-01 Ku70‐knockout mice, in contrast, appear to be tumor prone and develop thymic lymphomas with high incidence (30, 36). Finally, in agreement with a Ku70‐specific role in life‐span regulation, it was recently shown that knockdown of Ku70, but not Ku80, significantly extended life span in the p53‐null background . 2020-10-27 Ku80 is a protein that, in humans, is encoded by the XRCC5 gene. Together, Ku70 and Ku80 make up the Ku heterodimer, which binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair.It is also required for V(D)J recombination, which utilizes the NHEJ pathway to promote antigen diversity in the mammalian immune system.

also been suggested that Ku80 has a Ku70-independent DNA DSB repair function, in addition to the one depen-dent on Ku70 (Koike and Koike 2005). Throughout our several studies on supernumerary (B) chromosomes (a kind of parasitic chromosomes), we consistently came across several effects of these chromosomes in the grasshopper Eyprepocnemis Ku70 and Ku80 proteins; X-ray crystallography Ku70 and Ku80 form a heterodimeric complex involved in multiple nuclear processes. This complex plays a key role in DNA repair due to its ability to bind DNA double-strand breaks and facilitate repair by the nonhomolo-gous end-joining pathway. Ku70 and Ku80 have been proposed to contain DNA-PKcs functions both within and outside of the damage response to effectively design therapeutic strategies. Ku70 and Ku80 (also called Ku86) are encoded by the XRCC6 and XRCC5 genes, respectively, in humans, and have a strong afﬁ nity for free ends of DNA ( 21 ). DNA-PKcs is a 469-kDa protein composed of several distinct functional domains Purification of the Ku70/Ku80 dimer.
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Despite recent advances in our understanding of the function of long noncoding RNAs (lncRNAs), their roles and functions in DNA repair pathways remain poorly understood. By screening a panel of uncharacterized lncRNAs to identify those whose transcription is induced by double-strand breaks (DSBs), w …. In eukaryotes, Ku is a heterodimer comprised of two subunits, Ku70 and Ku80, that is best characterized for its central role as the initial DNA end binding factor in the “classical” non-homologous end joining (C-NHEJ) pathway, the main DNA double-strand break (DSB) repair pathway in mammals.

av P Håkansson · 2006 — regarding the function of an alternative mammalian RNR small subunit, and on the role of is the binding of the end-binding Ku70/Ku80 complex, leading to the. Pia C. Maly Sundgren, 2017 Sep 12, Neuroimaging: Anatomy Meets Function. Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal av P Umate · 2011 · Citerat av 90 — The role of these motifs in ATP-binding, ATP-hydrolysis (ATPase), RNA A total of 31 DNA helicases (like RecQ members, KU70, MCM Protection of Kidney Function with Human Antioxidation Protein Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in 22 jan.
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First, either Ku70 or Ku80 functions outside the Ku heterodimer such that deletion of one is not identical to deletion of the other. Second, divergent genetic backgrounds or environments inﬂuence the phenotype. To distinguish between these possi-bilities, the Ku70 and Ku80 mutations were crossed together to generate Ku70, Ku80, and double-mutant mice

Two isoforms of Ku80 encoded by the same genes, namely, Ku80 and KARP-1 are expressed and function in primate cells, but not in rodent cells. Heterodimers of the 70 and 80 kDa Ku autoantigens (Ku70 and Ku80) activate the DNA‐dependent protein kinase (DNA‐PK). Mutations in any of the three subunits of this protein kinase (Ku70, Ku80 and DNA‐PKcs) lead to sensitivity to ionizing radiation (IR) and to DNA double‐strand breaks, and V(D)J recombination product formation defects. centromeric function of Ku70 was not observed in 14 other grasshopper and locust species, or in the mouse, thus suggesting that it is an autapomorphy in E. plorans.

14 Sep 2020 of the Ku70/80 heterodimer in vitro. We further defined the function of the Ku70 and Ku80 C-terminal domains in DNA end binding and

DNA-PKcs is a 469-kDa protein composed of several distinct functional domains Purification of the Ku70/Ku80 dimer. Ku70 and Ku80 were purified from the HeLa nuclear extract (CilBiotech, Mons, Belgium) by using a combination of heparin, double‐stranded DNA cellulose, phenyl sepharose high resolution and monoQ chromatographies.

Although Ku70 is proposed as a candidate for a … Structural Basis of Importin-α-Mediated Nuclear Transport for Ku70 and Ku80 Agnes A. S. Takeda1, Andrea C. de Barros1, Chiung-Wen Chang2, Boštjan Kobe2 and Marcos R. M. Fontes1⁎ 1Departamento de Física e Biofísica, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP 18618-970, Brazil 2School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience 2003-03-01 of the Ku70/80 heterodimer in vitro. We further deﬁned the function of the Ku70 and Ku80 C-terminal domains in DNA end binding and DNA-PKCS interaction. 2. Results 2.1. The Enhanced Cyan Fluorescent Protein (ECFP)-Ku70/EYFP-Ku80 FRET Pair The Ku70/80 heterodimer binds to DNA ends as a starting point for NHEJ complex assembly and juxtaposition Both Ku70 and Ku80 therefore contain monopartite NLSs, and sequences outside the basic cluster make favorable interactions with Impα, suggesting that this may be a general feature in monopartite NLSs. We show that the Ku70 NLS has a higher affinity for Impα than the Ku80 NLS, consistent with more extensive interactions in its N-terminal region.