DNA ligase III and DNA ligase IV carry out genetically distinct forms of end joining in human somatic cells.
DNA Repair (Amst)
; 21: 97-110, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24837021
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 KuLIGIII and KuLIGIV (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.
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Base de dados:
MEDLINE
Assunto principal:
DNA Ligases
/
Reparo do DNA por Junção de Extremidades
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article