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DNA excision repair. Which of the following is the type of DNA repair in which thymine dimers are directly broken down by the enzyme photolyase?
In a direct repair, thymine dimers are directly broken down by the enzyme photolyase. It is used to identify mutants with restored biosynthetic activity.
Why is it more likely that insertions or deletions will be more detrimental to a cell than point mutations? Envision that each is a section of a DNA molecule that has separated in preparation for transcription, so you are only seeing the template strand. What type of mutation is each? Figure from: P arker, et al Microbiology from Openstax In recent years, scientific interest has been piqued by the discovery of a few individuals from northern Europe who are resistant to HIV infection.
Back to the Top It is used to identify newly formed auxotrophic mutants. It is used to identify spontaneous mutants. It is used to identify mutants lacking photoreactivation activity. Think about It Why is it more likely that insertions or deletions will be more detrimental to a cell than point mutations?
World Health Organization. Accessed August 5, DNA oxidation. In Wikipedia, The Free Encyclopedia. AP site. Benzo a pyrene. Pyrimidine dimer. It is notable that the proteins encoded by these human DNA repair genes are closely related to proteins encoded by yeast RAD genes, indicating that nucleotide -excision repair is highly conserved throughout eukaryotes.
With cloned yeast and human repair genes available, it has been possible to purify their encoded proteins and develop in vitro systems to study the repair process. Although some steps remain to be fully elucidated, these studies have led to the development of a basic model for nucleotide -excision repair in eukaryotic cells.
In mammalian cells, the XPA protein and possibly also XPC initiates repair by recognizing damaged DNA and forming complexes with other proteins involved in the repair process. This cleavage excises an oligonucleotide consisting of approximately 30 bases. An intriguing feature of nucleotide -excision repair is its relationship to transcription.
A connection between transcription and repair was first suggested by experiments showing that transcribed strands of DNA are repaired more rapidly than nontranscribed strands in both E. Since DNA damage blocks transcription, this transcription-repair coupling is thought to be advantageous by allowing the cell to preferentially repair damage to actively expressed genes. The stalled RNA polymerase is recognized by a protein called transcription-repair coupling factor, which displaces RNA polymerase and recruits the UvrABC excinuclease to the site of damage.
Although the molecular mechanism of transcription -repair coupling in mammalian cells is not yet known, it is noteworthy that the XPB and XPD helicases are components of a multisubunit transcription factor called TFIIH that is required to initiate the transcription of eukaryotic genes see Chapter 6.
Thus, these helicases appear to be required for the unwinding of DNA during both transcription and nucleotide -excision repair, providing a direct biochemical link between these two processes.
Patients suffering from Cockayne's syndrome are also characterized from a failure to preferentially repair transcribed DNA strands, suggesting that the proteins encoded by the two genes known to be responsible for this disease CSA and CSB function in transcription-coupled repair.
In addition, one of the genes responsible for inherited breast cancer in humans BRCA1 appears to encode a protein specifically involved in transcription-coupled repair of oxidative DNA damage, suggesting that defects in this type of DNA repair can lead to the development of one of the most common cancers in women.
A third excision repair system recognizes mismatched bases that are incorporated during DNA replication. Many such mismatched bases are removed by the proofreading activity of DNA polymerase. The ones that are missed are subject to later correction by the mismatch repair system, which scans newly replicated DNA. If a mismatch is found, the enzymes of this repair system are able to identify and excise the mismatched base specifically from the newly replicated DNA strand, allowing the error to be corrected and the original sequence restored.
Since methylation occurs after replication, newly synthesized DNA strands are not methylated and thus can be specifically recognized by the mismatch repair enzymes. Mismatch repair is initiated by the protein MutS, which recognizes the mismatch and forms a complex with two other proteins called MutL and MutH.
MutL and MutS then act together with an exonuclease and a helicase to excise the DNA between the strand break and the mismatch, with the resulting gap being filled by DNA polymerase and ligase. Mismatch repair in E. The mismatch repair system detects and excises mismatched bases in newly replicated DNA, which is distinguished from the parental strand because it has not yet been methylated.
MutS binds to the mismatched base, followed by more Eukaryotes have a similar mismatch repair system, although the mechanism by which eukaryotic cells identify newly replicated DNA differs from that used by E. In mammalian cells, it appears that the strand-specificity of mismatch repair is determined by the presence of single-strand breaks which would be present in newly replicated DNA in the strand to be repaired Figure 5.
The eukaryotic homologs of MutS and MutL then bind to the mismatched base and direct excision of the DNA between the strand break and the mismatch, as in E. The importance of this repair system is dramatically illustrated by the fact that mutations in the human homologs of MutS and MutL are responsible for a common type of inherited colon cancer hereditary nonpolyposis colorectal cancer, or HNPCC. The relationship between HNPCC and defects in mismatch repair was discovered in , when two groups of researchers cloned the human homolog of MutS and found that mutations in this gene were responsible for about half of all HNPCC cases.
Subsequent studies have shown that most of the remaining cases of HNPCC are caused by mutations in one of three human genes that are homologs of MutL. Mismatch repair in mammalian cells. Mismatch repair in mammalian cells is similar to E.
MutS and MutL bind to the mismatched base more The direct reversal and excision repair systems act to correct DNA damage before replication, so that replicative DNA synthesis can proceed using an undamaged DNA strand as a template.
Should these systems fail, however, the cell has alternative mechanisms for dealing with damaged DNA at the replication fork. Pyrimidine dimers and many other types of lesions cannot be copied by the normal action of DNA polymerases, so replication is blocked at the sites of such damage. Downstream of the damaged site, however, replication can be initiated again by the synthesis of an Okazaki fragment and can proceed along the damaged template strand Figure 5.
The result is a daughter strand that has a gap opposite the site of damage to the parental strand. One of two types of mechanisms may be used to repair such gaps in newly synthesized DNA: recombinational repair or error-prone repair. Postreplication repair. The presence of a thymine dimer blocks replication, but DNA polymerase can bypass the lesion and reinitiate replication at a new site downstream of the dimer.
The result is a gap opposite the dimer in the newly synthesized DNA more Recombinational repair depends on the fact that one strand of the parental DNA was undamaged and therefore was copied during replication to yield a normal daughter molecule see Figure 5. The undamaged parental strand can be used to fill the gap opposite the site of damage in the other daughter molecule by recombination between homologous DNA sequences see the next section.
Because the resulting gap in the previously intact parental strand is opposite an undamaged strand, it can be filled in by DNA polymerase. Although the other parent molecule still retains the original damage e. By a similar mechanism, recombination with an intact DNA molecule can be used to repair double strand breaks, which are frequently introduced into DNA by radiation and other damaging agents.
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