DNA Replication and Synthesis

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Questions and Answers

What is the primary function of telomerase during DNA replication?

To add simple repeat sequences to the 3' end of telomeric DNA (correct)

To repair DNA errors during lagging-strand synthesis

To initiate leading-strand synthesis

To remove RNA primers from the 3' end of telomeric DNA

What is the mechanism by which telomerase adds simple repeat sequences to telomeric DNA?

By binding to the 5' end of telomeric DNA

By synthesizing DNA in the 5' to 3' direction

By using an RNA primer to initiate lagging-strand synthesis (correct)

By removing RNA primers from the 3' end of telomeric DNA

What is the role of the RNA carried by telomerase during DNA replication?

To initiate transcription

To match the 3' DNA end and allow its extension (correct)

To repair DNA errors during replication

To act as a primer for leading-strand synthesis

What is the approximate risk of error during DNA replication?

10^-6 Signup and view all the answers

What is the effectiveness of DNA repair systems in correcting errors during DNA replication?

99% Signup and view all the answers

What is the primary reason why DNA replication is not 100% accurate?

Inherent errors during DNA synthesis Signup and view all the answers

What is the purpose of DNA repair systems during DNA replication?

To correct errors during DNA synthesis Signup and view all the answers

What is the result of inaccurate DNA replication?

Mutations and potential disease Signup and view all the answers

What is a prominent type of photoproduct detected in UV-irradiated DNA?

Intrastrand dimers consisting of two pyrimidine bases joined by a cyclobutane ring structure Signup and view all the answers

What is the process by which a damaged base is directly changed to a normal one?

Photolysis Signup and view all the answers

What is the purpose of the enzyme O6-alkylguanine alkyltransferase?

To remove alkyl groups from O6-alkylguanine residues Signup and view all the answers

What is the result of the mispairing of O6-methylguanine with thymine in a DNA duplex?

A GC to AT transition Signup and view all the answers

What happens to the O6-alkylguanine alkyltransferase enzyme after it has transferred an alkyl group?

It becomes inactivated Signup and view all the answers

What is the type of DNA damage that can be repaired by the enzymes alkyltransferase and photolysis?

Pyrimidine dimers Signup and view all the answers

What is the difference between direct and indirect DNA repair?

Direct repair changes a damaged base to a normal one, while indirect repair removes a damaged base and replaces it with a new one Signup and view all the answers

What is the type of DNA damage that is repaired by the enzymes involved in the process of NHEJ?

Double-strand breaks Signup and view all the answers

What is the direction of polymerase movement on the leading strand during DNA replication?

From the 5' terminus to the 3' terminus Signup and view all the answers

What is the role of DNA ligase in lagging strand synthesis?

To join Okazaki fragments to high-molecular-weight DNA Signup and view all the answers

What is the term for the short fragments synthesized during lagging strand synthesis?

Okazaki fragments Signup and view all the answers

What is the direction of polymerase movement on the lagging strand during DNA replication?

Opposite to the direction of fork movement Signup and view all the answers

Who proposed the concept of discontinuous DNA synthesis?

Reiji Okazaki Signup and view all the answers

What is the function of primase during DNA replication?

To rebind to single-strand template DNA Signup and view all the answers

What is the structure of the DNA polymerase shown in the diagram?

A holoenzyme Signup and view all the answers

What is the significance of the IP and AID domains in DNA polymerase γ?

They are involved in DNA binding Signup and view all the answers

What is the primary consequence of 8-oxoguanine pairing with adenine?

It introduces a strongly mutagenic alteration in DNA. Signup and view all the answers

What is the primary function of the MutT protein?

To hydrolyze 8-oxo-dGTP and prevent its incorporation into DNA. Signup and view all the answers

What is the consequence of MutT's action on 8-oxo-dGTP?

It prevents the incorporation of 8-oxoguanine into DNA during replication. Signup and view all the answers

What is the role of MutM in countering the mutagenic effect of 8-oxoguanine?

It excises 8-oxoguanine from a C-G base pair to initiate base excision repair. Signup and view all the answers

What is the primary function of the MutY protein?

To excise A from an A-oG base pair in another BER process. Signup and view all the answers

What is the significance of the structure of human OGG1?

It completely excludes guanine from the catalytic pocket. Signup and view all the answers

How does the mismatch repair system identify the newly replicated daughter strand in E. coli?

By recognizing the absence of methylation on the daughter strand. Signup and view all the answers

What is the consequence of MutY's action on A-oG base pairs?

It allows for the correction of errors during the next round of replication. Signup and view all the answers

What is the role of the Dam methylase in the replication process?

It methylates the A residue in the GATC sequence after DNA replication Signup and view all the answers

What is the characteristic of tumor cells from individuals with HNPCC?

They exhibit microsatellite instability Signup and view all the answers

What is the function of DNA mismatch repair?

To correct errors in DNA replication Signup and view all the answers

What is the typical outcome of DNA polymerase slippage at microsatellite regions?

An increase in the number of repeating units Signup and view all the answers

What is the likely response to a blocking DNA lesion in the leading strand template?

Replication fork regression Signup and view all the answers

What is the result of replication fork regression?

A heteroduplex with a short loop Signup and view all the answers

What is the function of nucleotide excision repair (NER)?

To recognize and repair DNA damage Signup and view all the answers

What is the consequence of a germ-line mutation in the genes for mismatch repair proteins?

Increased risk of HNPCC Signup and view all the answers

Study Notes

DNA Replication

Primase rebinding to single-strand template DNA begins a new primer.
Discontinuous DNA synthesis: the leading strand is extended continuously, while the lagging strand is synthesized in short fragments (Okazaki fragments) that are later joined by DNA ligase.

Proteins in Eukaryotic DNA Replication

The structure of human DNA polymerase γ (pol γ) and T7 phage DNA polymerase holoenzymes show two unique domains (IP and AID) involved in DNA binding.

Fidelity of DNA Replication

Telomerase adds simple repeat sequences to the 3’ end of telomeric DNA, allowing lagging-strand synthesis followed by ligation and RNA removal.
The RNA carried by telomerase matches the 3’ DNA end, allowing its extension.
The crystal structure of the telomerase catalytic subunit from the red flour beetle shows DNA and telomerase RNA modeled into the large central cleft.

DNA Repair

DNA replication is not error-free, with a risk of error of 10-6 to 10-8.
DNA repair systems correct errors in 99% of cases.
Structures of pyrimidine dimer photoproducts, including thymine dimers, are formed when UV-irradiated DNA or DNA from a UV-irradiated organism is examined.
DNA can be repaired directly or indirectly, by changing a damaged base to a normal one or replacing a DNA segment containing the damaged nucleotide.

Types of DNA Repair

Direct repair: photolysis (use of light energy to repair pyrimidine dimers) and alkyltransferase (enzymes that are inactivated after one catalytic cycle)
Indirect repair: single-strand damages (BER, NER, MMR) and double-strand breaks (NHEJ)

Alkylation Damage

O6-methylguanine, a highly mutagenic product, can form a mispair with thymine, leading to a GC à AT transition.
Repair of alkylation damage involves the enzyme O6-alkylguanine alkyltransferase, which transfers a methyl or ethyl group from an O6–methylguanine or O6-ethylguanine residue to a cysteine residue in the active site of the protein.

Oxidation Damage

8-oxoguanine, a strongly mutagenic alteration, forms readily with adenine and can lead to GC à AT or AT à GC transversions.
MutT is a nucleotidase that cleaves 8-oxo-dGTP, the dNTP of 8-oxoguanine, to the corresponding nucleoside monophosphate, “sanitizing” cellular dNTP pools.
MutM, mutT, and mutY gene products work together to counter the mutagenic effect of 8-oxoguanine.

Mismatch Repair

Mutations in mismatch repair proteins were found in tumor cells from individuals with an inherited cancer predisposition called HNPCC (heritable nonpolyposis colon cancer).
Germ-line mutations in the genes for five different mismatch repair proteins have been found to be associated with HNPCC.
Tumor cells from those affected with HNPCC exhibit microsatellite instability, a large number of mutations in regions of the genome containing repeats of single-, double-, and triple-nucleotide sequences.
DNA mismatch repair is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination.

Nucleotide Excision Repair (NER)

NER is a process for repairing DNA damage, including UV-induced damage.
Replication fork regression is a likely response to a blocking DNA lesion in the leading strand template.

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Description

Learn about the process of DNA replication, including discontinuous DNA synthesis and the role of primase and other proteins at the replication fork.