Human DNA Ligase IV and the Ligase IV/XRCC4 Complex: Analysis of Nick Ligation Fidelity
نویسندگان
چکیده
منابع مشابه
Chlorella virus DNA ligase: nick recognition and mutational analysis.
Chlorella virus PBCV-1 DNA ligase seals nicked DNA substrates consisting of a 5'-phosphate-terminated strand and a 3'-hydroxyl-terminated strand annealed to a bridging DNA template strand. The enzyme discriminates at the DNA binding step between substrates containing a 5'-phosphate versus a 5'-hydroxyl at the nick. Mutational analysis of the active site motif KxDGxR (residues 27-32) illuminates...
متن کاملKinetic mechanism and fidelity of nick sealing by Escherichia coli NAD+-dependent DNA ligase (LigA).
Escherichia coli DNA ligase (EcoLigA) repairs 3'-OH/5'-PO4 nicks in duplex DNA via reaction of LigA with NAD(+) to form a covalent LigA-(lysyl-Nζ)-AMP intermediate (step 1); transfer of AMP to the nick 5'-PO4 to form an AppDNA intermediate (step 2); and attack of the nick 3'-OH on AppDNA to form a 3'-5' phosphodiester (step 3). A distinctive feature of EcoLigA is its stimulation by ammonium ion...
متن کاملImpact of DNA ligase IV on the fidelity of end joining in human cells.
A DNA ligase IV (LIG4)-null human pre-B cell line and human cell lines with hypomorphic mutations in LIG4 are significantly impaired in the frequency and fidelity of end joining using an in vivo plasmid assay. Analysis of the null line demonstrates the existence of an error-prone DNA ligase IV-independent rejoining mechanism in mammalian cells. Analysis of lines with hypomorphic mutations demon...
متن کاملLigase I and ligase III mediate the DNA double-strand break ligation in alternative end-joining.
In eukaryotes, DNA double-strand breaks (DSBs), one of the most harmful types of DNA damage, are repaired by homologous repair (HR) and nonhomologous end-joining (NHEJ). Surprisingly, in cells deficient for core classic NHEJ factors such as DNA ligase IV (Lig4), substantial end-joining activities have been observed in various situations, suggesting the existence of alternative end-joining (A-EJ...
متن کاملSingle-stranded DNA ligation and XLF-stimulated incompatible DNA end ligation by the XRCC4-DNA ligase IV complex: influence of terminal DNA sequence
The double-strand DNA break repair pathway, non-homologous DNA end joining (NHEJ), is distinctive for the flexibility of its nuclease, polymerase and ligase activities. Here we find that the joining of ends by XRCC4-ligase IV is markedly influenced by the terminal sequence, and a steric hindrance model can account for this. XLF (Cernunnos) stimulates the joining of both incompatible DNA ends an...
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ژورنال
عنوان ژورنال: Biochemistry
سال: 2007
ISSN: 0006-2960,1520-4995
DOI: 10.1021/bi0621516