MIMS Summary: DNA Structure

DNA Structure

• DNA strands are joined by phosphodiester bonds
• Negatively charged phosphates face outwards
• One turn of the helix occurs every 10.5 bases in B-DNA
• The rise per base pair is 3.4Å, and the width of the helix is 20Å
• The rise per helical turn is 10.5 x 3.4Å

B-DNA and A-DNA

• B-DNA is the most common form, while dsRNA adopts the A form
• A-form is wider than B-form, with a more compressed major groove, wider minor groove, and tilted bases
• GC-rich DNA adopts the A form

Z-DNA

• Z-DNA is a left-handed DNA structure, with a phosphate backbone that follows a zigzag trajectory

Chromatin Structure

• Chromatin is formed by chromosomal DNA bound to proteins like histones and other DNA-packaging factors
• The basic unit of chromatin is the nucleosome
• The nucleosome core particle consists of a sequence of 146nt wrapped around a barrel-shaped octamer of histone in 1.7 turns of a left-handed superhelix

Histones

• Histones are positively charged
• The histone octamer of the NCP particle consists of 2 H2A-H2B dimers flanking a tetramer of 2 H3 and H4
• Amino-terminal tails of histones project and can be modified, leading to compaction of chromatin and control of gene transcription

Chromatin Fibre

• 10nm fibre is the most abundant chromatin form, with nucleosomes separated by linker DNA
• The repeat length of nucleosomes is 200nt
• 10nm fibre can transition to 30nm fibre (regular/compact form), with most folds being random

DNA Loop Formation

• DNA loops are the next stage in the organisation of DNA, anchored to a protein-chromosome scaffold
• DNA loops are segregated from the genome and bring enhancers and promoters together, playing an important role in gene regulation during development and differentiation

Structural Maintenance of Chromosomes (SMC) Proteins

• Cohesin and condensin are SMC proteins with split ATPase domains
• Two SMC proteins hinge dimerise to give a V-shape
• Role in DNA loop formation
• Cohesin and condensin heads are linked by a non-SMC subunit, forming a topological ring that traps DNA and forms a loop

Topologically Associated Domain (TAD)

• TAD is a constituent unit of chromosomal DNA at the Mb scale
• TAD is a separate transcriptional/topological entity
• TAD is formed by several DNA loops folding together

Chromosome Territory

• Chromosome territory is a unique volume occupied by each chromosome in the nucleus
• Chromosome territory is divided into compartments A and B
• Compartment A is euchromatin, while compartment B is heterochromatin

Chromatin Status

• Chromatin status is a dynamic state of chromatin (open/close etc.) and can be modified by the binding of H1, leading to compaction
• Post-translational modification of histone tails can also modify chromatin status
• Chromatin remodelers alter the position of nucleosomes
• Lysine acetylation to histone tails reduces overall positive charge, reducing chromatin compaction
• Histone tail modifications represent an epigenetic histone code, which is dynamic due to chromatin writer/eraser proteins
• Nucleosome remodelling shifts nucleosome position to allow availability of DNA-binding sites