DNA Repair and Immune Receptor Recombination: HR, NHEJ, V(D)J

loss of heterozygosity

HR causes loss of functioning copy of gene

HR cons

loss of heterozygosity, too little HR

Strand invasion

A single-stranded DNA region enters a homologous DNA duplex and pairs with its complementary strand

Heteroduplex

DNA duplex containing strands originating from two different DNA molecules

Resection

Removal of nucleotides from the ends of broken DNA to produce single-stranded overhangs

NHEJ

Recognition and binding > Complex formation > End processing > Gap filling > Ligation

HR

Resection > Strand invasion > DNA synthesis > Release & repairing > gap filling > Ligation

Exonuclease

resects the 5′ ends, creating 3′ overhangs

Endonuclease

Cleaves internal phosphodiester bonds

RecA

eukayrote recombinase enzyme

Replication-fork collapse

turn a single-strand nick into a DSB

Strand invasion relies on

sequence similarity and complementary base pairing

BRCA1/BRCA2

help recruit Rad51 and support HR

meiotic recombination enzymes

Spo11, Mre11

Holliday junction

A branch point where four DNA strands are connected during recombination

Gene conversion

Mismatch repair can convert one allele into another

HR during meiosis

crossover or non-crossover

vertical resolution

crossover

horizontal resolution

non-crossover

antibody

unbound BCR

TCR recognition

major histocompatibility complex (MHC)

BCR recognition

shape of an intact antigen

Hypervariable regions

antigen binding site

site of b cell rearrangement

bone marrow

site of t cell rearrangement

Thymus

Heavy and beta

V-D-J

light and alpha

V-J

12/23 rule

Recombination occurs between RSS sites with different spacer lengths

DNA to immune function

DNA sequence → amino acid sequence → protein folding and shape → antigen-binding specificity.