DNA Damage

**What do cell cycle checkpoints control?** -

They control the progression of the cell through the cell cycle, ensuring proper division.

**What happens if the cell detects damage at a checkpoint?** -

The cell undergoes "arrest" to fix the damage or "apoptosis" if the damage is irreparable.

**Where are the major cell cycle checkpoints located?** -

At G1/S (restriction point), G2, and M phase.

**Which cell cycle checkpoint is the most critical?** -

The G1/S checkpoint, as passing through it commits the cell to division.

**What happens if a cell passes through the G1/S checkpoint?** -

It is committed to division, and DNA replication must be completed, or apoptosis will occur.

**What is G0 in the cell cycle?** -

A quiescent state where the cell exits the cycle and does not divide.

**Can cells re-enter the cell cycle from G0?** -

Yes, they can re-enter if needed, such as skin cells responding to a cut.

**What is DNA damage?** -

A chemical alteration of the structure or topology of DNA.

**How can DNA damage lead to mutation?** -

Damage can cause changes in the nucleotide base composition.

**What is the function of p53 in response to DNA damage?** -

p53 is a transcription factor and tumor suppressor that accumulates to stop the cell cycle for repair or trigger apoptosis if damage is too extensive.

**What happens when p53 activates genes in response to DNA damage?** -

The cell cycle is arrested to allow damage repair, or apoptosis occurs if the damage is irreparable.

**What type of substances cause DNA damage through alkylation?** -

Electrophilic substances that seek electrons.

**What are examples of alkylating agents that damage DNA?** -

EMS (ethyl methanesulfonate), aflatoxin (from Aspergillus mold, found in peanuts), and nitrogen/sulfur mustards (chemical warfare agents).

**How have mustard agents been repurposed in medicine?** -

Some mustard agents are used as chemotherapy drugs because they cause DNA damage in rapidly dividing cancer cells.

**How do electrophilic agents damage DNA?** -

By adding methyl or ethyl groups to slightly charged regions on DNA.

**Why is DNA highly negatively charged?** -

The phosphate groups in DNA carry a negative charge, and nitrogenous bases have partially charged regions.

**What do electrophilic substances do to DNA?** -

They add alkyl groups (methyl or ethyl) to charged regions on DNA, leading to damage.

**What is a common site of alkylation on DNA?** -

The N3 position of adenine, forming 3-methyl adenine (3mA).

**Why is 3-methyl adenine (3mA) harmful to DNA replication?** -

It is a non-coding base that cannot hydrogen bond, preventing base pairing during replication.

**What happens if 3-methyl adenine (3mA) is present during replication?** -

It disrupts replication, leading to apoptosis, making it cytotoxic.

**What is a common methylation site on guanine that leads to mutations?** -

The O6 position of guanine.

**Why is O6-methylguanine mutagenic?** -

It prevents guanine from forming three hydrogen bonds with cytosine, leading to incorrect base pairing.

**What happens when guanine is methylated at the O6 position?** -

It can only form two hydrogen bonds and pairs with thymine instead of cytosine.

**What mutation results from O6-methylguanine formation?** -

A GC base pair is converted into an AT base pair during the next round of replication.

**What chemical is known to cause O6-methylguanine formation?** -

EMS (ethyl methanesulfonate), an alkylating agent used in DNA damage studies.

**How does UV radiation damage DNA?** -

It causes pyrimidines on the same strand to form thymine dimers.

**What are thymine dimers?** -

Adjacent thymines on the same DNA strand hydrogen bond to each other instead of their complementary bases.

**How do thymine dimers affect DNA structure?** -

They create a bulge in the DNA strand, disrupting base pairing.

**Why are thymine dimers problematic for DNA replication?** -

They block replication because polymerases cannot properly read the damaged region.

**How can cells bypass thymine dimer damage during replication?** -

Some specialized polymerases use error-free bypass by inserting adenines (A) across from the unreadable region.

**What is the primary cause of skin cancer?** -

UV radiation.

**How does ozone protect against UV radiation?** -

It blocks harmful UV rays from reaching Earth's surface.

**What caused the depletion of the ozone layer?** -

Chlorofluorocarbons (CFCs) used in freon for air conditioners and freezers.

**How did ozone depletion affect skin cancer rates?** -

More UV radiation entered the atmosphere, leading to increased skin cancer cases in the early 2000s.

**What happened to the ozone layer by 2018?** -

The ozone hole was gone due to bans on freon production.

**How does skin cancer develop at the molecular level?** -

DNA damage accumulates enough mutations to disrupt cell cycle control.

**Why is early detection of melanoma important?** -

Early-stage melanoma is treatable, but late detection becomes more deadly.

**How do gamma and X-rays damage DNA?** -

They ionize water molecules surrounding DNA, creating free radicals.

**What are free radicals?** -

Neutral molecules with an unpaired valence electron that can damage DNA.

**What are two examples of free radicals that damage DNA?** -

Hydroxide (•OH) and superoxide (O₂•⁻) radicals.

**What types of DNA damage can free radicals cause?** -

Single-stranded breaks, double-stranded breaks, or broken chromosomes.

**What real-world case involved oxidative DNA damage?** -

The case in *Erin Brockovich*, where hexavalent chromium from a chemical plant caused oxidative damage.