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PDBsum entry 5ei9
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Transcription/DNA
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PDB id
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5ei9
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References listed in PDB file
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Key reference
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Title
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Structural basis for human prdm9 action at recombination hot spots.
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Authors
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A.Patel,
J.R.Horton,
G.G.Wilson,
X.Zhang,
X.Cheng.
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Ref.
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Genes Dev, 2016,
30,
257-265.
[DOI no: ]
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PubMed id
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Abstract
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The multidomain zinc finger (ZnF) protein PRDM9 (PRD1-BF1-RIZ1 homologous
domain-containing 9) is thought to influence the locations of recombination hot
spots during meiosis by sequence-specific DNA binding and trimethylation of
histone H3 Lys4. The most common variant of human PRDM9, allele A (hPRDM9A),
recognizes the consensus sequence 5'-NCCNCCNTNNCCNCN-3'. We cocrystallized
ZnF8-12 of hPRDM9A with an oligonucleotide representing a known hot spot
sequence and report the structure here. ZnF12 was not visible, but ZnF8-11, like
other ZnF arrays, follows the right-handed twist of the DNA, with the α helices
occupying the major groove. Each α helix makes hydrogen-bond (H-bond) contacts
with up to four adjacent bases, most of which are purines of the complementary
DNA strand. The consensus C:G base pairs H-bond with conserved His or Arg
residues in ZnF8, ZnF9, and ZnF11, and the consensus T:A base pair H-bonds with
an Asn that replaces His in ZnF10. Most of the variable base pairs (N) also
engage in H bonds with the protein. These interactions appear to compensate to
some extent for changes from the consensus sequence, implying an adaptability of
PRDM9 to sequence variations. We investigated the binding of various alleles of
hPRDM9 to different hot spot sequences. Allele C was found to bind a C-specific
hot spot with higher affinity than allele A bound A-specific hot spots, perhaps
explaining why the former is dominant in A/C heterozygotes. Allele L13 displayed
higher affinity for several A-specific sequences, allele L9/L24 displayed lower
affinity, and allele L20 displayed an altered sequence preference. These
differences can be rationalized structurally and might contribute to the
variation observed in the locations and activities of meiotic recombination hot
spots.
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