DNA Repair

sources of dna damage

intrinsic sources:

• errors in replciation

• incorrect bases paired

• deaminate (water attack causing cytosine —> uracil)

• depurinate (loss of puring base)

extrinsic:

• chemical agents

• UV radiation

types of mutations

point mutations

• transitions: purine to purine, pyrmidine to pyrimidine

• transversion: pyrimidine to purine, vice versa

insertions deletions

• single nucleotide inserted/removed

• big chromosomosals misarranged

mismatch base repair (MMR)

fixes incorrect base pair matches

• MutS forms sliding clamp (dimer) on DNA and distorts it to find mismatches

• whole strand is removed and filled by repair polymerases

Prokarytoes

• have methylases that add CH3 to mark parental strand

• MutS cuts off unmethylated strand

Eukarytoes

• have nicks in new synthesized strands, those are cute off

base excision repair (BER)

fixes damaged bases (deaminated, depurinated)

1. damage recognition through glycolases

2. remove whole strand

3. dna synthesis using undamage strand as template

4. repair ligase fill gap in former damage strand

nucleotide excision repair (NER)

dixes bulky abduct, thymine dimers, interstrand crosslinks that distort dna structure

• protein xbc recognizes damage

double strand break repair (DSBR)

NHEJ

• glues ends together

• in G1, G0 phase

• error prone

HR

• uses sister chromatids to find correct sequence

• G2/ S phase

• error free

cancer chemotherapeutics - why dna damage effective to treat cancer

damage the dna so badly they cant divide any further