Molecular Biology BIOL 4310-12

Spontaneous Mutation

DNA damage happens naturally and randomly and are usually linked to normal biological or chemical processes in the organism

Induced Mutation

DNA damage resulting from the influence of external factors, can cause chemical or physical damage

Mutagen

Natural or artificial agents that cause mutation

What can cause point mutations?

replication errors of damage to bases

What can hydrolysis cause?

Deamination and depurination, leading to potential point mutations

What can reactive oxygen cause?

Oxidative damage, which can lead to potential point mutations

What can Nitrous acid cause?

Deamination of A and C nucleotides, leading to point mutations; causes transition mutations

What can spontaneous mutation occur in?

DNA replication and aerobic respiration

What can alkylating agents cause?

Adding alkyl groups to nucleotides, leading to point mutations, can alter or prevent base pairing

What can radiation cause?

interbase cross-links and strand breaks

What can UV light cause?

Can form pyrimidine dimers that distort the DNA helix and stall DNA polymerase during replication

What can X-rays and Gamma rays cause?

Single strand and double strand DNA breaks

What type of mutagens are base analogs and intercalating agents and what do each do?

-Chemical mutagens

-Base analogs substitute for nucleotides

-Intercalating agents distort the DNA helix

What are DNA-damaging agents used in?

Chemotherapy

What doe Mismatch Repair [MMR] fix

Point mutations and small indels

How does Mismatch repair fix replication errors?

Use lack of methylation to identify and distinguish the new strand from the parent strand

What is an issue with Mismatch repair?

Costly process in terms of energy required

What is the mechanism of Mismatch repair?

-Mismatch detected on new DNA strand [MutS and MutL]

-DNA strand is cut, removing mismatched nucleotide and neighbors [MutH and Helicase II]

-DNA Polymerase II replaces gap with correct nucleotides

-DNA Ligase seals the gap

What is a common cause of hereditary nonpolyposis colorectal cancer [HNPCC]

Mutations [Inherited loss of function mutation] in an allele of MMR genes MLH1 or MSH2

How does Direct Repair correct a damaged nucleotide?

In one step, restoring altered nucleotides to original [correct] structures

What does methylguanine transferase do in direct repair

Direct repair of O^6-methylguanine to Guanine

What happens with photoreactivation of pyrimidine dimers?

DNA photolyase performs the direct repair of pyrimidine dimers

What does Base Excision Repair [BER] do?

Repairs subtle distortions in DNA

What does DNA Glycosylase do in Base Excision Repair

Recognizes damaged base and severs it from sugar

What does AP endonuclease do in Base Excision Repair

Nicks the DNA backbone

What does polymerase do in Base Excision Repair

Removes and replaces DNA segment and ligase seals the nick

What does Nucleotide Excision Repair [NER] do

Repairs bulky distortions [lesions] in DNA

What does excinuclease do in Nucleotide Excision repair

makes strand incisions on either side of the region

What does transcription coupled repair do in nucleotide excision repair?

DNA damage is recognized by stalled RNA polymerase