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Download fileHolliday Junctions Formed from Human Telomeric DNA
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posted on 16.10.2018, 00:00 by Shozeb Haider, Pengfei Li, Soraia Khiali, Deeksha Munnur, Arvind Ramanathan, Gary N. ParkinsonCells have evolved inherent mechanisms,
like homologous recombination
(HR), to repair damaged DNA. However, repairs at telomeres can lead
to genomic instability, often associated with cancer. While most rapidly
dividing cells employ telomerase, the others maintain telomere length
through HR-dependent alternative lengthening of telomeres (ALT) pathways.
Here we describe the crystal structures of Holliday junction intermediates
of the HR-dependent ALT mechanism. Using an extended human telomeric
repeat, we also report the crystal structure of two Holliday junctions
in close proximity, which associate together through strand exchange
to form a hemicatenated double Holliday junction. Our combined structural
results demonstrate that ACC nucleotides in the C-rich lagging strand
(5′-CTAACCCTAA-3′) at the telomere
repeat sequence constitute a conserved structural feature that constrains
crossover geometry and is a preferred site for Holliday junction formation
in telomeres.
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Holliday junctionscrystal structuretelomere lengthHolliday Junctionscrystal structuresstrand exchangecrossover geometryHuman Telomeric DNA CellsHolliday junction intermediatesHolliday junction formationACC nucleotidesHR-dependent alternativeHR-dependent ALT mechanismgenomic instabilityCTAACTAHolliday junction