Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
DNA Repair (Amst)
2014 Sep 01;21:97-110. doi: 10.1016/j.dnarep.2014.04.015.
Show Gene links
Show Anatomy links
DNA ligase III and DNA ligase IV carry out genetically distinct forms of end joining in human somatic cells.
Oh S
,
Harvey A
,
Zimbric J
,
Wang Y
,
Nguyen T
,
Jackson PJ
,
Hendrickson EA
.
???displayArticle.abstract???
Ku-dependent C-NHEJ (classic non-homologous end joining) is the primary DNA EJing (end joining) repair pathway in mammals. Recently, an additional EJing repair pathway (A-NHEJ; alternative-NHEJ) has been described. Currently, the mechanism of A-NHEJ is obscure although a dependency on LIGIII (DNA ligase III) is often implicated. To test the requirement for LIGIII in A-NHEJ we constructed a LIGIII conditionally-null human cell line using gene targeting. Nuclear EJing activity appeared unaffected by a deficiency in LIGIII as, surprisingly, so were random gene targeting integration events. In contrast, LIGIII was required for mitochondrial function and this defined the gene's essential activity. Human Ku:LIGIII and Ku:LIGIV (DNA ligase IV) double knockout cell lines, however, demonstrated that LIGIII is required for the enhanced A-NHEJ activity that is observed in Ku-deficient cells. Most unexpectedly, however, the majority of EJing events remained LIGIV-dependent. In conclusion, although human LIGIII has an essential function in mitochondrial maintenance, it is dispensable for most types of nuclear DSB repair, except for the A-NHEJ events that are normally suppressed by Ku. Moreover, we describe that a robust Ku-independent, LIGIV-dependent repair pathway exists in human somatic cells.
Andres,
A human XRCC4-XLF complex bridges DNA.
2012, Pubmed
Andres,
A human XRCC4-XLF complex bridges DNA.
2012,
Pubmed
Arakawa,
Functional redundancy between DNA ligases I and III in DNA replication in vertebrate cells.
2012,
Pubmed
,
Xenbase
Audebert,
Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining.
2004,
Pubmed
Bennardo,
Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair.
2008,
Pubmed
Bentley,
DNA ligase I null mouse cells show normal DNA repair activity but altered DNA replication and reduced genome stability.
2002,
Pubmed
Bentley,
DNA ligase I is required for fetal liver erythropoiesis but is not essential for mammalian cell viability.
1996,
Pubmed
Bentley,
DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining.
2004,
Pubmed
Boboila,
Classical and alternative end-joining pathways for repair of lymphocyte-specific and general DNA double-strand breaks.
2012,
Pubmed
Bunting,
End-joining, translocations and cancer.
2013,
Pubmed
Caldecott,
Mammalian single-strand break repair: mechanisms and links with chromatin.
2007,
Pubmed
Caldecott,
An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III.
1994,
Pubmed
,
Xenbase
Cheng,
Ku counteracts mobilization of PARP1 and MRN in chromatin damaged with DNA double-strand breaks.
2011,
Pubmed
Cottarel,
A noncatalytic function of the ligation complex during nonhomologous end joining.
2013,
Pubmed
Doherty,
Hyperactive piggyBac gene transfer in human cells and in vivo.
2012,
Pubmed
Ellenberger,
Eukaryotic DNA ligases: structural and functional insights.
2008,
Pubmed
Fattah,
Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells.
2010,
Pubmed
Fattah,
Ku70, an essential gene, modulates the frequency of rAAV-mediated gene targeting in human somatic cells.
2008,
Pubmed
Frosina,
Two pathways for base excision repair in mammalian cells.
1996,
Pubmed
Gao,
DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair.
2011,
Pubmed
,
Xenbase
Ghosal,
DNA damage tolerance: a double-edged sword guarding the genome.
2013,
Pubmed
Guirouilh-Barbat,
Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends.
2007,
Pubmed
Göttlich,
Rejoining of DNA double-strand breaks in vitro by single-strand annealing.
1998,
Pubmed
,
Xenbase
Hartlerode,
Mechanisms of double-strand break repair in somatic mammalian cells.
2009,
Pubmed
Hladnik,
Variable expression of HPRT deficiency in 5 members of a family with the same mutation.
2008,
Pubmed
Huang,
DNA crosslinking damage and cancer - a tale of friend and foe.
2013,
Pubmed
Kass,
Collaboration and competition between DNA double-strand break repair pathways.
2010,
Pubmed
Katyal,
Disconnecting XRCC1 and DNA ligase III.
2011,
Pubmed
,
Xenbase
Khan,
AAV-mediated gene targeting methods for human cells.
2011,
Pubmed
Kohli,
Facile methods for generating human somatic cell gene knockouts using recombinant adeno-associated viruses.
2004,
Pubmed
Krokan,
Base excision repair.
2013,
Pubmed
Lakshmipathy,
The human DNA ligase III gene encodes nuclear and mitochondrial proteins.
1999,
Pubmed
,
Xenbase
Le Chalony,
Partial complementation of a DNA ligase I deficiency by DNA ligase III and its impact on cell survival and telomere stability in mammalian cells.
2012,
Pubmed
,
Xenbase
Liang,
Human DNA ligases I and III, but not ligase IV, are required for microhomology-mediated end joining of DNA double-strand breaks.
2008,
Pubmed
,
Xenbase
Lieber,
The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway.
2010,
Pubmed
Mahaney,
XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair.
2013,
Pubmed
Mansour,
Hierarchy of nonhomologous end-joining, single-strand annealing and gene conversion at site-directed DNA double-strand breaks.
2008,
Pubmed
Mao,
DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells.
2008,
Pubmed
Mattarucchi,
Microhomologies and interspersed repeat elements at genomic breakpoints in chronic myeloid leukemia.
2008,
Pubmed
McVey,
MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings.
2008,
Pubmed
Miller,
Large-scale analysis of adeno-associated virus vector integration sites in normal human cells.
2005,
Pubmed
Mladenov,
Induction and repair of DNA double strand breaks: the increasing spectrum of non-homologous end joining pathways.
2011,
Pubmed
Nakai,
Large-scale molecular characterization of adeno-associated virus vector integration in mouse liver.
2005,
Pubmed
Nussenzweig,
A backup DNA repair pathway moves to the forefront.
2007,
Pubmed
Oh,
Human LIGIV is synthetically lethal with the loss of Rad54B-dependent recombination and is required for certain chromosome fusion events induced by telomere dysfunction.
2013,
Pubmed
Pacchierotti,
Mechanisms and risk of chemically induced aneuploidy in mammalian germ cells.
2006,
Pubmed
Paul,
DNA ligases I and III cooperate in alternative non-homologous end-joining in vertebrates.
2013,
Pubmed
,
Xenbase
Perez-Jannotti,
Two forms of mitochondrial DNA ligase III are produced in Xenopus laevis oocytes.
2001,
Pubmed
,
Xenbase
Puebla-Osorio,
Early embryonic lethality due to targeted inactivation of DNA ligase III.
2006,
Pubmed
,
Xenbase
Rass,
Role of Mre11 in chromosomal nonhomologous end joining in mammalian cells.
2009,
Pubmed
Roy,
XRCC4's interaction with XLF is required for coding (but not signal) end joining.
2012,
Pubmed
Ruhanen,
Involvement of DNA ligase III and ribonuclease H1 in mitochondrial DNA replication in cultured human cells.
2011,
Pubmed
,
Xenbase
Schulte-Uentrop,
Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks.
2008,
Pubmed
Seluanov,
DNA end joining becomes less efficient and more error-prone during cellular senescence.
2004,
Pubmed
Simsek,
DNA ligase III: a spotty presence in eukaryotes, but an essential function where tested.
2011,
Pubmed
,
Xenbase
Simsek,
Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair.
2011,
Pubmed
,
Xenbase
Simsek,
DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation.
2011,
Pubmed
,
Xenbase
Simsek,
Alternative end-joining is suppressed by the canonical NHEJ component Xrcc4-ligase IV during chromosomal translocation formation.
2010,
Pubmed
Tsai,
Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity.
2008,
Pubmed
Verkaik,
Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells.
2002,
Pubmed
Wang,
Ku86 represses lethal telomere deletion events in human somatic cells.
2009,
Pubmed
Wang,
DNA ligase III as a candidate component of backup pathways of nonhomologous end joining.
2005,
Pubmed
Wang,
PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways.
2006,
Pubmed
Weterings,
The Ku80 carboxy terminus stimulates joining and artemis-mediated processing of DNA ends.
2009,
Pubmed
Windhofer,
Low levels of DNA ligases III and IV sufficient for effective NHEJ.
2007,
Pubmed
Xie,
Role of mammalian Mre11 in classical and alternative nonhomologous end joining.
2009,
Pubmed
Yano,
Functional significance of the interaction with Ku in DNA double-strand break recognition of XLF.
2011,
Pubmed
You,
DNA damage and decisions: CtIP coordinates DNA repair and cell cycle checkpoints.
2010,
Pubmed
Zha,
Mre11: roles in DNA repair beyond homologous recombination.
2009,
Pubmed
Zhang,
An essential role for CtIP in chromosomal translocation formation through an alternative end-joining pathway.
2011,
Pubmed
Zheng,
Okazaki fragment maturation: nucleases take centre stage.
2011,
Pubmed
Zhuang,
Exonuclease function of human Mre11 promotes deletional nonhomologous end joining.
2009,
Pubmed
