Chemistry Reference
In-Depth Information
Figure 6.4
Nonhomologous end-joining mechanism in mammalian cells
The major NHEJ pathway (Figure 6.4) relies on a set of core proteins. The two
DNA ends of the double-strand break are recognized and bound by the ring-shaped
heterodimer Ku70/Ku80,which recruits the DNA-dependent protein kinase cata-
lytic subunit (DNA-PKcs).
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The assembled DNA-dependent protein kinase (DNA-
PK) holoenzyme then exhibits serine - threonine protein kinase and DNA end - bridging
activities.
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Among other functions, the kinase activity regulates DNA end access to
processing enzymes like the DNA-PKcs-associated Artemis nuclease.
31,32
Finally, the
XRCC4/DNA ligase IV complex is responsible for the ligation step.
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Another core
NHEJ factor is Cernunnos-XLF, a factor with a predicted structural similarity to
XRCC4 that has been identifi ed as an XRCC4-interacting protein.
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DNA polymer-
ases l and m (Table 6.2 ) fi ll gaps during NHEJ.
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Homologous Recombination Repair
HRR acts on double-strand breaks generated at broken replication forks or occur-
ring within replicated DNA. Recombinational repair requires the presence of an
identical or nearly identical sequence to be used as a template for repair of the
break. The enzymatic machinery responsible for this repair process is nearly identi-
cal to the machinery responsible for chromosomal crossover during meiosis. This
pathway allows a damaged chromosome to be repaired using a sister chromatid or
a homologous chromosome as a template.
