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Holliday junctions formed from human telomeric DNA

DOI: 10.1021/jacs.8b08699 DOI Help

Authors: Shozeb Haider (University College London) , Pengfei Li (University College London) , Soraia Khiali (University College London) , Deeksha Munnur (University of Oxford) , Arvind Ramanathan (Oak Ridge National Laboratory) , Gary N. Parkinson (University of London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of The American Chemical Society

State: Published (Approved)
Published: October 2018
Diamond Proposal Number(s): 12305 , 9204

Abstract: Cells 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 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 and forms 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.

Subject Areas: Chemistry, Biology and Bio-materials

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I24-Microfocus Macromolecular Crystallography

Added On: 23/10/2018 10:57

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)