Ku protein: Difference between revisions
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=== Ku Ring === | === Ku Ring === | ||
The <scene name='56/567269/Ku_ring/1'>Ku Ring</scene> is composed of a broad base of beta barrels that cradle the DNA, and a narrow bridge that serves to protect the double strand break from base pairing with other DNA base pairs and degradation <ref name="Walker"/>. There is little interaction between the ring and the backbone or base pairs of DNA; instead, the ring associates with DNA by the cradle fitting into the major grooves of the helix <ref name="Walker"/>. The positive electrostatic charge caused by polarization of the ring also allows the negatively charged backbone of DNA to be guided into the correct position <ref name="Walker"/> | The <scene name='56/567269/Ku_ring/1'>Ku Ring</scene> is composed of a broad base of beta barrels that cradle the DNA, and a narrow bridge that serves to protect the double strand break from base pairing with other DNA base pairs and degradation <ref name="Walker"/>. There is little interaction between the ring and the backbone or base pairs of DNA; instead, the ring associates with DNA by the cradle fitting into the major grooves of the helix <ref name="Walker"/>. The positive electrostatic charge caused by polarization of the ring also allows the negatively charged backbone of DNA to be guided into the correct position <ref name="Walker"/>. The Ku protein also has a high affinity to DNA due to its form being preset for the helix. As a result of the asymmetric ring, there is a strong preference (Kd value of 1.5 to 4 X 10^-10 M<ref name="Walker"/>) for the Ku ring to slide onto the ends of DNA <ref name="Walker"/>. In addition, other asymmetric features, such as a abundance of Asp residues on the N terminus of the Ku Ring, prevent the Ku protein from sliding further on the DNA helix. While wrapping over the entire helix, the Ku ring is thin over the bridge, allowing ligases and polymerases to efficiently interact in [http://en.wikipedia.org/wiki/Non-homologous_end_joining non-homologous end joining (NHEJ)]. <ref name="Walker"/> | ||
== Domains == | == Domains == | ||
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=== α/β-Domain === | === α/β-Domain === | ||
Contained inside the <scene name='56/567269/Ku70_dimer/2'>α/β-Domain</scene> is a [ | Contained inside the <scene name='56/567269/Ku70_dimer/2'>α/β-Domain</scene> is a [http://en.wikipedia.org/wiki/Rossman_fold Rossman fold] at the N terminus that is used to bind nucleotides in DNA.<ref name="Walker"/> | ||
In terms of protein structure, the α/β-Domain contributes little to the dimer interface between the subunits. | In terms of protein structure, the α/β-Domain contributes little to the dimer interface between the subunits. | ||
The C terminus of the domain can be bound to other repair molecules, using the α/β-Domain as a scaffold.<ref name="Walker"/> | The C terminus of the domain can be bound to other repair molecules, using the α/β-Domain as a scaffold.<ref name="Walker"/> | ||
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The <scene name='56/567269/Ku70_dimer/6'>DNA binding ring</scene> on the open end of DNA is associated with the Ku70 subunit. | The <scene name='56/567269/Ku70_dimer/6'>DNA binding ring</scene> on the open end of DNA is associated with the Ku70 subunit. | ||
By binding DNA, Ku realigns the the strands and protects the molecule from degradation and unwanted bonds while NHEJ occurs.<ref name="Walker"/> | By binding DNA, Ku realigns the the strands and protects the molecule from degradation and unwanted bonds while NHEJ occurs.<ref name="Walker"/> | ||
The regulation of the DNA binding ring of Ku is still under research, with data supporting oxidative stress and redox reactions decreasing the association of the Ku heterodimer with bound DNA through alterations in cysteine residues on the Ku70 subunit | The regulation of the DNA binding ring of Ku is still under research, with data supporting oxidative stress and redox reactions decreasing the association of the Ku heterodimer with bound DNA through alterations in cysteine residues on the Ku70 subunit. <ref name="source3"/> <ref name="source4"> PMID: 14585978</ref> | ||