2bcv: Difference between revisions

Revision as of 17:36, 21 February 2008

DNA polymerase lambda in complex with Dttp and a DNA duplex containing an unpaired Dtmp

OverviewOverview

Insertions and deletions in coding sequences can alter the reading frame of genes and have profound biological consequences. In 1966, Streisinger proposed that these mutations result from strand slippage, which in repetitive sequences generates misaligned intermediates stabilized by correct base pairing that support polymerization. We report here crystal structures of human DNA polymerase lambda, which frequently generates deletion mutations, bound to such intermediates. Each contains an extrahelical template nucleotide upstream of the active site. Surprisingly, the extra nucleotide, even when combined with an adjacent mismatch, does not perturb polymerase active site geometry, which is indistinguishable from that for correctly aligned strands. These structures reveal how pol lambda can polymerize on substrates with minimal homology during repair of double-strand breaks and represent strand-slippage intermediates consistent with Streisinger's classical hypothesis. They are thus relevant to the origin of single-base deletions, a class of mutations that can confer strong biological phenotypes.

About this StructureAbout this Structure

2BCV is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase., Garcia-Diaz M, Bebenek K, Krahn JM, Pedersen LC, Kunkel TA, Cell. 2006 Jan 27;124(2):331-42. PMID:16439207

Page seeded by OCA on Thu Feb 21 16:36:27 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2bcv.gif|left|200px]]<br />
+[[Image:2bcv.gif|left|200px]]<br /><applet load="2bcv" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2bcv" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2bcv, resolution 2.00&Aring;" />
 '''DNA polymerase lambda in complex with Dttp and a DNA duplex containing an unpaired Dtmp'''<br />
 ==Overview==
-Insertions and deletions in coding sequences can alter the reading frame, of genes and have profound biological consequences. In 1966, Streisinger, proposed that these mutations result from strand slippage, which in, repetitive sequences generates misaligned intermediates stabilized by, correct base pairing that support polymerization. We report here crystal, structures of human DNA polymerase lambda, which frequently generates, deletion mutations, bound to such intermediates. Each contains an, extrahelical template nucleotide upstream of the active site., Surprisingly, the extra nucleotide, even when combined with an adjacent, mismatch, does not perturb polymerase active site geometry, which is, indistinguishable from that for correctly aligned strands. These, structures reveal how pol lambda can polymerize on substrates with minimal, homology during repair of double-strand breaks and represent, strand-slippage intermediates consistent with Streisinger's classical, hypothesis. They are thus relevant to the origin of single-base deletions, a class of mutations that can confer strong biological phenotypes.
+Insertions and deletions in coding sequences can alter the reading frame of genes and have profound biological consequences. In 1966, Streisinger proposed that these mutations result from strand slippage, which in repetitive sequences generates misaligned intermediates stabilized by correct base pairing that support polymerization. We report here crystal structures of human DNA polymerase lambda, which frequently generates deletion mutations, bound to such intermediates. Each contains an extrahelical template nucleotide upstream of the active site. Surprisingly, the extra nucleotide, even when combined with an adjacent mismatch, does not perturb polymerase active site geometry, which is indistinguishable from that for correctly aligned strands. These structures reveal how pol lambda can polymerize on substrates with minimal homology during repair of double-strand breaks and represent strand-slippage intermediates consistent with Streisinger's classical hypothesis. They are thus relevant to the origin of single-base deletions, a class of mutations that can confer strong biological phenotypes.
 ==About this Structure==
-BCV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, NA and TTP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BCV OCA].
+BCV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=TTP:'>TTP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BCV OCA].
 ==Reference==
@@ Line 16: / Line 15: @@
 [[Category: Bebenek, K.]]
 [[Category: Garcia-Diaz, M.]]
-[[Category: Krahn, J.M.]]
+[[Category: Krahn, J M.]]
-[[Category: Kunkel, T.A.]]
+[[Category: Kunkel, T A.]]
-[[Category: Pedersen, L.C.]]
+[[Category: Pedersen, L C.]]
 [[Category: MG]]
 [[Category: NA]]
@@ Line 30: / Line 29: @@
 [[Category: streisinger]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:01:12 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:36:27 2008''