DNA repair

pg. 267-275

Ilkka Koskela

Katri Vilkman

Foreword

DNA• variation is an essential

factor to evolution (1000-10^6 lesions per day)

• stability is important for the individual (less than 1/1000 mutations are permanent)

• A relatively large amount of genes are devoted to coding DNA repair functions.

Sources of damage:• heat• metabolic accidents

(free radicals) • radiation (UV, X-Ray)• exposure to

substances (especially aromatic compounds)

Types of damage:• deamination of

nucleotides• depurination of

nucleotides• oxidation of bases• breaks in DNA

strands

Diseases

• colon cancer • cellular ultraviolet

sensitivity• Werner syndrome

(premature aging, retarded growth)

• Bloom syndrome (sunlight hypersensitivity)

Damage of the double helix

• Single strand damage– information is still

backed up in the other strand

• Double strand damage– no backup– can cause the

chromosome to break up

Single strand repair 1/2

• Base excision repair– A base-specific DNA

glycosylase detects an altered base and removes it

– AP endonuclease and phosphodiesterase remove sugar phosphate

– DNA Polymerase fills and DNA ligase seals the nick

Single strand repair 2/2

• Nucleotide excision repair– a large multienzyme

compound scans the DNA strand for anomalities

– upon detection a nuclease cuts the strand on both sides of the damage

– DNA helicase removes the oligonucleotide

– the gap is repaired by DNA polymerase and DNA ligase enzymes

Double strand repair 1/2

• Nonhomologous end-joining– only in emergency

situations– two broken ends of DNA

are joined together– a couple of nucleotides

are cut from both of the strands

– ligase joins the strands together

Double strand repair 2/2

• Homologous end-joining– damaged site is copied

from the other chromosome by special recombination proteins

DNA repair enzymes

• a lot of DNA damage -> elevated levels of repair enzymes

• extreme change in cell's environment (heat, UV, radiation) activates genes that code DNA repair enzymes– For an example, heat-shock

proteins are produced in heat-shock response when being subjected to high temperatures.

Cell Cycle and DNA repair

• Cell cycle is delayed if there is a lot of DNA damage.

• Repairing DNA as well as signals sent by damaged DNA delays progression of cell cycle.

->ensures that DNA damages are repaired before the cell divides

References• Pictures

– http://www.2modern.com/index.asp?PageAction=VIEWPROD&ProdID=985– http://www.senescence.info/WS.jpg– http://en.wikipedia.org/wiki/Dna– http://www.funpecrp.com.br/gmr/year2003/vol1-2/imagens/sim0001fig1.jpg– http://www.science.siu.edu/microbiology/micr460/PageMill%20Images/image32.gif– http://www.bio.brandeis.edu/haberlab/jehsite/images/nhejd.gif– http://www.biochemsoctrans.org/bst/029/0655/bst0290655f02.gif– http://www.antigenics.com/products/tech/hsp/images/animation.jpg– http://bioinformatics.psb.ugent.be/images/illust_cell_cycle_large.jpg

• Information– Alberts et al: Molecular Biology of the Cell, 2002, 4th ed– http://en.wikipedia.org/wiki/Dna_repair