12.6 DNA Repair12.6 DNA Repair

DNA RepairDNA Repair Errors in DNA replication Errors in DNA replication or or damagedamage to DNA to DNA

create mutations create mutations - May result in cancer - May result in cancer

Fortunately, Fortunately, mostmost errors and damage are errors and damage are repairedrepaired

Type of repair depends upon the type of Type of repair depends upon the type of damage or errordamage or error

Organisms vary in their ability to repair DNAOrganisms vary in their ability to repair DNA

What damages DNA?What damages DNA?

DNA DNA polymerasepolymerase proofreads DNA, but proofreads DNA, but repair enzymesrepair enzymes correct errors in other correct errors in other ways.ways.

Types of DNA RepairTypes of DNA Repair

In many modern species, three types of In many modern species, three types of DNA repair peruse the genetic material DNA repair peruse the genetic material

1) Photoreactivation repair1) Photoreactivation repair

2) Excision repair2) Excision repair

3) Mismatch repair3) Mismatch repair

Photoreactivation RepairPhotoreactivation Repair

Photoreactivation repairPhotoreactivation repair uses light energy uses light energy to split to split pyrimidine dimerspyrimidine dimers that that kinkkink the the DNA.DNA.Pyrimidine dimersPyrimidine dimers - bonds between C’s - bonds between C’s

and/or T’s on the same strand.and/or T’s on the same strand.PhotoPhotolyases - lyases - enzymes enzymes that absorb light that absorb light

energy and use it to energy and use it to detectdetect and and bind bind to to pyrimidine dimers, then pyrimidine dimers, then breakbreak the extra bond. the extra bond.

Humans Humans do not do not have this type of repairhave this type of repair

Excision RepairExcision Repair

Pyrimidine dimers and surrounding Pyrimidine dimers and surrounding bases are removed and the area is filled bases are removed and the area is filled in correctly.in correctly.Enzymes cut the bond between the Enzymes cut the bond between the sugar sugar

and baseand base and snip out (excise) the and snip out (excise) the pyrimidine dimerpyrimidine dimer..

DNA polymeraseDNA polymerase fills in the correct fills in the correct nucleotides.nucleotides.

Mismatch RepairMismatch Repair

Mismatch repairMismatch repair proofreads newly proofreads newly replicated DNA for replicated DNA for loopsloops that that indicate indicate noncomplemetarynoncomplemetary base pairing base pairing

The incorrect base is excised and The incorrect base is excised and replaced.replaced.

Mutations in repair genes cause Mutations in repair genes cause disorders characterized by disorders characterized by broken broken chromosomeschromosomes and and increased risk of increased risk of cancercancer..

Figure 12.4

Repair Disorders: Trichothiodystrophy

Photosensitivity, Icthyosis, Brittle hair and nails, Intellectual impairment, Decreased fertility and Short stature.

At least five genes are involved

Symptoms reflect accumulating oxidative damage

Faulty nucleotide excision repair or base excision repair or both

Mild case

Figure 12.4

Repair Disorders:Inherited Colon Cancer

Hereditary nonpolyposis colon cancer

Affects 1/200 individuals

Defect in mismatch repair

HNPCC gene is on chromosome 2

Figure 12.4

Repair Disorders:Xeroderma Pigmentosum

• Autosomal recessive; Seven genes involved

• Malfunction of excision repair

• Thymine dimers remain and block replication

• Must avoid sunlight• Only 250 cases

worldwide

Figure 12.4

Repair Disorders:Ataxia Telangiectasis

• Autosomal recessive disorder• Defect in cell cycle checkpoint kinase• Cells continue through cell cycle without

pausing to inspect DNA• Individuals with AT have 50X the risk of

developing cancer over general population• Heterozygotes have a two- to sixfold

increase in cancer risk