Medical School · Year 1 · Foundations · includes a quiz and discussion video

Lecture 10: DNA Structure and Replication

Unit 1.1: Foundations of Medicine & Medical Sciences

Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the structure of DNA including the double helix, base pairing rules, and antiparallel orientation
2. Explain the semi-conservative mechanism of DNA replication
3. Identify the key enzymes and proteins involved in DNA replication and their functions
4. Describe the differences between leading and lagging strand synthesis
5. Identify common types of DNA damage and explain the major DNA repair mechanisms
6. Describe clinical conditions resulting from defects in DNA replication or repair

DNA Structure

Discovery and Historical Context

The structure of DNA represents one of the most celebrated discoveries in the history of biology. In 1953, James Watson and Francis Crick proposed the double helix model, building upon critical X-ray crystallography data produced by Rosalind Franklin and Maurice Wilkins. Their model elegantly explained Erwin Chargaff's earlier observation that in any DNA sample, the amount of adenine equals thymine, and the amount of guanine equals cytosine. This insight into complementary base pairing immediately suggested how genetic information could be copied faithfully. Watson, Crick, and Wilkins received the Nobel Prize in 1962 for this discovery, though Franklin's crucial contributions were tragically unrecognized due to her untimely death from cancer in 1958.

Components of DNA

DNA is a polymer built from nucleotide subunits, each containing three components. The deoxyribose sugar provides the structural backbone, named for its missing oxygen atom at the 2' carbon compared to ribose. The phosphate group links adjacent nucleotides through the formation of phosphodiester bonds. The nitrogenous bases carry the genetic information and come in two structural varieties: the purines (adenine and guanine), which have two fused rings, and the pyrimidines (cytosine and thymine), which have single rings. A useful mnemonic is that the "pure" purines (A and G) have "pure as gold" two rings, while the "pyrimidines" (C, T, U) "cut" their structure down to one.

Nucleotide Linkage and Backbone Structure

Nucleotides connect through phosphodiester bonds that link the 5' phosphate group of one nucleotide to the 3' hydroxyl group of the next. This creates the sugar-phosphate backbone that runs along the outside of the helix. The backbone carries a negative charge due to the ionized phosphate groups, which is why DNA migrates toward the positive electrode during gel electrophoresis. This consistent directionality means every DNA strand has a 5' end (with a free phosphate) and a 3' end (with a free hydroxyl group).

<image>Panel A: Single nucleotide with deoxyribose sugar carbons numbered 1' through 5', phosphate group (orange) at 5' position, adenine base (blue) at 1' position. Panel B: Two nucleotides connected by phosphodiester bond with 5'-to-3' directional arrows. Panel C: Bond formation highlighted in yellow showing 3'-OH linking to 5'-phosphate with water release. Panel D: Complete chemical structure with all atoms and bonds explicitly shown.</image>

The Double Helix

DNA adopts a right-handed helical structure known as B-DNA under physiological conditions. Two polynucleotide strands wind around each other in an antiparallel arrangement—one strand runs 5' to 3' while its partner runs 3' to 5'. The nitrogenous bases project inward toward the helical axis where they form hydrogen bonds with bases on the opposite strand. The sugar-phosphate backbones spiral along the outside, creating the double helix's characteristic twisted ladder appearance.

The helix makes one complete turn every 10.5 base pairs, spanning 3.4 nanometers in length. Individual base pairs are separated by 0.34 nanometers. These precise measurements mean that a single human cell, if its DNA were stretched end to end, would extend approximately two meters—yet it packs into a nucleus only 6 micrometers in diameter.

Base pairing follows strict complementarity rules. Adenine always pairs with thymine through two hydrogen bonds, while guanine pairs with cytosine through three hydrogen bonds. This difference in hydrogen bonding explains why GC-rich regions of DNA are more thermally stable and require higher temperatures to "melt" (denature) the strands apart. The complementary nature of base pairing also explains how DNA can be faithfully copied: each strand contains all the information needed to reconstruct its partner.

<image>Panel A: B-DNA segment showing three full turns with blue and red strands emphasizing antiparallel orientation, 5' and 3' arrows at each end. Panel B: Major groove (wider) and minor groove (narrower) labeled with dimension indicators. Panel C: A-T base pair with two dashed hydrogen bonds and G-C pair with three hydrogen bonds. Panel D: Chemical structures of bases with color-coded atoms (carbon gray, nitrogen blue, oxygen red, hydrogen white).</image>

Major and Minor Grooves

The helical twist of DNA creates two grooves of different widths that spiral along the molecule. The major groove is wider and more accessible, providing a surface where proteins can read the sequence of bases without unwinding the helix. Many transcription factors and other regulatory proteins recognize specific DNA sequences by inserting alpha helices or other structural motifs into the major groove, where the edges of the base pairs present a distinctive pattern of hydrogen bond donors and acceptors. The minor groove is narrower and less information-rich, though certain drugs and proteins do bind here.

Organization of Genetic Information

Genome Size and Content

The human genome contains approximately 3 billion base pairs distributed across 23 pairs of chromosomes. Despite this vast amount of DNA, only about 20,000 genes encode proteins, and the protein-coding sequences (exons) comprise merely 1.5% of the total genome. The remaining DNA includes introns (non-coding sequences within genes), regulatory regions that control gene expression, and vast stretches of repetitive sequences whose functions are still being discovered. This organization means that most DNA does not directly encode proteins but may serve structural, regulatory, or as-yet-unknown roles.

DNA Packaging

Fitting two meters of DNA into a microscopic nucleus requires extraordinary compaction. The first level of packaging involves wrapping DNA around histone proteins to form nucleosomes, which resemble beads on a string. Each nucleosome contains approximately 147 base pairs of DNA wrapped around an octamer of histone proteins. Nucleosomes compact into a 30-nanometer chromatin fiber, which further folds and loops to form chromosomes visible during cell division. Human cells contain 46 chromosomes organized as 23 homologous pairs—22 pairs of autosomes plus two sex chromosomes.

DNA Replication: Overview

Fundamental Concepts

DNA replication follows three key principles that ensure accurate inheritance of genetic information. First, replication is semi-conservative: each daughter molecule contains one strand from the parent molecule and one newly synthesized strand. This was elegantly demonstrated by Meselson and Stahl in 1958 using density-labeled DNA. Second, replication is bidirectional, proceeding in both directions from each origin of replication. Third, replication is semi-discontinuous—one strand is synthesized continuously while the other must be made in short fragments that are later joined together.

Replication Origins

Replication begins at specific sites called origins of replication, where initiator proteins recognize and bind particular DNA sequences. Prokaryotes like E. coli have a single origin called oriC, from which two replication forks proceed around the circular chromosome until they meet on the opposite side. Eukaryotes, with their much larger genomes, employ multiple origins on each chromosome—sometimes thousands—allowing replication to complete within a reasonable timeframe. Each origin generates a replication bubble that expands bidirectionally until adjacent bubbles merge.

<image>Panel A: Original parent DNA molecule with both strands colored purple, arrows showing bidirectional replication fork movement. Panel B: Replication in action with original strands separating and new orange strands synthesizing from each template. Panel C: Two complete daughter molecules, each with one purple (original) and one orange (newly synthesized) strand. Panel D: Color-coded key with annotations explaining semi-conservative half-conservation from parent.</image>

The Replication Machinery

Initiator Proteins and Helicase

Replication begins when initiator proteins recognize and bind the origin of replication, recruiting other components of the replication machinery. The enzyme DNA helicase plays a crucial early role by unwinding the double helix at the replication fork. Helicase uses the energy from ATP hydrolysis to break the hydrogen bonds between base pairs, separating the two strands and creating single-stranded regions that can serve as templates. Helicase travels along one strand, typically moving in the 5' to 3' direction, progressively unzipping the DNA ahead of the replication machinery.

Single-Strand Binding Proteins

Once helicase separates the DNA strands, single-strand binding proteins (SSBPs) immediately coat the exposed single-stranded DNA. These proteins serve multiple functions: they prevent the separated strands from re-annealing with each other, protect the single-stranded DNA from degradation by cellular nucleases, and help maintain the extended conformation needed for efficient copying. SSBPs bind cooperatively, meaning the binding of one protein facilitates the binding of adjacent proteins along the strand.

Topoisomerases

Unwinding the double helix creates a topological problem. As helicase separates the strands, the DNA ahead of the replication fork becomes increasingly overwound, creating positive supercoils that would eventually halt replication. Topoisomerase enzymes resolve this tension by temporarily cutting the DNA, allowing it to relax, and then resealing the break. Topoisomerase I cuts one strand, allows rotation around the intact strand, and religates the nick. Topoisomerase II (also called DNA gyrase in bacteria) cuts both strands, passes another segment of DNA through the gap, and reseals the break. These enzymes are critical targets for antibiotics (fluoroquinolones inhibit bacterial gyrase) and cancer chemotherapy agents (topoisomerase inhibitors like etoposide).

<image>Panel A: Y-shaped replication fork with intact double helix on left, separated strands on right, helicase (green hexameric ring) at junction with ATP and movement arrows. Panel B: Single-strand binding proteins (small blue ovals) coating both separated strands. Panel C: DNA ahead of fork showing positive supercoiling with plus signs indicating increasing twist. Panel D: Topoisomerase (red enzyme) cutting and religating DNA to relieve tension with directional arrows.</image>

Primase

DNA polymerases face a fundamental limitation: they cannot initiate DNA synthesis on a bare template. They can only add nucleotides to an existing 3' hydroxyl group. To solve this problem, cells employ primase, an RNA polymerase that can initiate synthesis de novo. Primase synthesizes short RNA primers (typically 10-12 nucleotides in prokaryotes, somewhat shorter in eukaryotes) that provide the 3'-OH group DNA polymerase requires. These RNA primers are later removed and replaced with DNA.

DNA Polymerase

DNA polymerase is the central enzyme of replication, catalyzing the synthesis of new DNA strands using the parental strands as templates. The enzyme reads the template in the 3' to 5' direction while synthesizing the new strand in the 5' to 3' direction—the only direction DNA polymerases can work. The reaction requires deoxynucleoside triphosphates (dATP, dGTP, dCTP, and dTTP), a template strand, a primer with a free 3'-OH, and magnesium ions as a cofactor.

Prokaryotes and eukaryotes use different but related DNA polymerases. In E. coli, DNA polymerase III is the main replicative enzyme, while DNA polymerase I removes primers and fills the resulting gaps. Eukaryotes use DNA polymerase alpha (Pol α) in association with primase to initiate synthesis, DNA polymerase epsilon (Pol ε) for leading strand synthesis, and DNA polymerase delta (Pol δ) for lagging strand synthesis.

DNA Ligase

The final step in replication requires DNA ligase, which seals the nicks in the sugar-phosphate backbone. This enzyme catalyzes the formation of phosphodiester bonds between adjacent nucleotides, requiring ATP (in eukaryotes and archaea) or NAD+ (in bacteria) as an energy source. Ligase is particularly important on the lagging strand, where it joins the many short fragments into a continuous strand.

<image>Panel A: Y-shaped replication fork with parental duplex splitting, helicase (green ring) unwinding DNA, SSBPs (blue ovals) coating single-stranded regions. Panel B: Leading strand with DNA polymerase III (orange) synthesizing continuously toward fork, 5' and 3' ends labeled. Panel C: Lagging strand showing primase (purple) making RNA primer (red wavy line), DNA polymerase III creating Okazaki fragment. Panel D: Completed Okazaki fragment with DNA ligase (yellow) sealing nick, arrows indicating synthesis and fork movement directions.</image>

Leading vs. Lagging Strand Synthesis

The Antiparallel Problem

Because DNA strands run antiparallel and DNA polymerase can only synthesize in the 5' to 3' direction, the two template strands present different challenges. One template runs 3' to 5' in the direction of fork movement, allowing its complement to be synthesized continuously. The other template runs 5' to 3' in the direction of fork movement, meaning its complement must be synthesized in the opposite direction of fork progression.

Leading Strand Synthesis

The leading strand uses the template oriented 3' to 5' (toward the fork), so the new strand can be synthesized continuously in the 5' to 3' direction as the fork advances. This strand requires only a single primer at the origin and then elongates smoothly as helicase unwinds more DNA. In eukaryotes, DNA polymerase epsilon handles leading strand synthesis with remarkable speed and accuracy.

Lagging Strand Synthesis

The lagging strand presents greater complexity because its template runs 5' to 3' toward the fork. The new strand must be synthesized in the opposite direction of fork movement, which is accomplished through discontinuous synthesis. As helicase exposes new template, primase synthesizes a primer, and DNA polymerase extends it until it reaches the previous fragment. These short segments are called Okazaki fragments (named after Reiji and Tsuneko Okazaki, who discovered them in the 1960s). In eukaryotes, Okazaki fragments are 100-200 nucleotides long; in prokaryotes, they can be 1,000-2,000 nucleotides.

Okazaki Fragment Processing

Converting the discontinuous lagging strand into a continuous strand requires several steps. After primase synthesizes an RNA primer, DNA polymerase extends it to create an Okazaki fragment. When the polymerase encounters the RNA primer of the preceding fragment, it either displaces the primer (creating a flap that is cleaved by FEN1 endonuclease) or the primer is removed by RNase H and DNA polymerase I (in prokaryotes). DNA polymerase then fills the gap with DNA, and finally DNA ligase seals the nick, creating a continuous strand.

<image>Panel A: Leading strand synthesis with single RNA primer (red) at origin, continuous DNA synthesis (blue) extending in fork movement direction. Panel B: Lagging strand with multiple RNA primers (red) at intervals, Okazaki fragments (blue) synthesized opposite to fork movement with 5' to 3' arrows. Panel C: Okazaki fragment maturation showing primer removal, gap filling, and ligase sealing the nick. Panel D: Final continuous lagging strand product with Okazaki fragment length measurement (100-200 nt in eukaryotes).</image>

Proofreading and Fidelity

Error Rates and Accuracy

The fidelity of DNA replication is remarkable. DNA polymerase initially incorporates an incorrect nucleotide about once every 100,000 bases (error rate of 10⁻⁵). Proofreading reduces this to about one error in 10 million bases (10⁻⁷). Post-replication mismatch repair further reduces the error rate to approximately one mistake per billion to 10 billion bases (10⁻⁹ to 10⁻¹⁰). Given that the human genome is 3 billion base pairs and is replicated completely with each cell division, this means only a few mutations accumulate per cell division.

Proofreading Mechanism

DNA polymerases possess an intrinsic proofreading capability through their 3' to 5' exonuclease activity. When an incorrect nucleotide is incorporated, it creates a mismatched base pair that distorts the DNA helix and does not fit properly in the polymerase's active site. This causes the polymerase to stall, and the newly incorporated (incorrect) nucleotide is transferred to the exonuclease active site, where it is cleaved off. The polymerase can then try again, inserting the correct nucleotide. This "editing function" dramatically improves replication fidelity.

<image>Panel A: Normal synthesis with polymerase (blue) adding correct G opposite template C, green checkmark indicating accuracy. Panel B: Error detection showing T-C mismatch causing helix distortion bulge, polymerase stalling with red stop sign. Panel C: 3' to 5' exonuclease activity removing mismatched T with directional arrow. Panel D: Correct G insertion with labeled exonuclease and polymerase domains on enzyme structure.</image>

Telomeres and the End Replication Problem

The Problem

Linear chromosomes present a unique challenge at their ends. On the lagging strand, when the final RNA primer is removed, there is no upstream primer to allow gap filling—the polymerase cannot synthesize DNA without a 3'-OH to extend from. This means that with each round of replication, the chromosome becomes slightly shorter. Without a solution, essential genes would eventually be lost and cell death would result.

Telomere Structure

Telomeres solve this problem by providing a buffer of non-coding repetitive sequence at chromosome ends. In humans, the telomeric repeat sequence is TTAGGG, reiterated approximately 2,500 times, creating a protective cap of roughly 15,000 base pairs. These sequences do not encode proteins, so their gradual shortening with each cell division does not immediately harm the cell. Telomeres also form specialized structures (T-loops) that protect chromosome ends from being recognized as DNA damage.

Telomerase

Certain cells can maintain or extend their telomeres using telomerase, a remarkable ribonucleoprotein enzyme. Telomerase carries its own RNA template (complementary to the telomeric repeat) and uses it to add telomeric sequences to the 3' end of chromosomes. This extension provides a template for primase and DNA polymerase to complete lagging strand synthesis closer to the chromosome end.

Telomerase is active in germ cells (ensuring that chromosomes passed to offspring are full-length), in stem cells (which need to divide many times), and in approximately 90% of cancer cells (contributing to their unlimited proliferative capacity). Most somatic cells have little or no telomerase activity, which is why they can only divide a limited number of times before telomere shortening triggers replicative senescence—the Hayflick limit.

<image>Panel A: End replication problem showing chromosome end with lagging strand template, RNA primer removal, unfillable gap, and resulting shortened daughter chromosome. Panel B: Telomere structure with TTAGGG repeat sequence (~2,500 repeats) and T-loop at chromosome end. Panel C: Telomerase (purple) with RNA template (AAUCCC, red) base-pairing with 3' overhang, extending by adding TTAGGG repeats. Panel D: Conventional DNA synthesis completing complementary strand after extension with directional arrows.</image>

Clinical Significance

Telomere biology has important clinical implications. Short telomeres are associated with cellular aging and may contribute to age-related diseases. Dyskeratosis congenita, a rare genetic disorder caused by mutations affecting telomerase or telomere maintenance proteins, is characterized by bone marrow failure, pulmonary fibrosis, and premature aging features. Conversely, the reactivation of telomerase in cancer cells is a key step in achieving cellular immortality, making telomerase an attractive therapeutic target. Several telomerase inhibitors are in clinical development as cancer treatments.

DNA Damage and Repair

Types of DNA Damage

DNA constantly experiences damage from both spontaneous chemical reactions and environmental exposures. Understanding these damage types and repair mechanisms is essential for understanding cancer, aging, and the action of many chemotherapy drugs.

Spontaneous damage occurs continuously through normal cellular chemistry. Depurination—the hydrolytic loss of purine bases (adenine or guanine)—occurs approximately 5,000 times per cell per day, leaving abasic sites. Deamination converts cytosine to uracil, which if unrepaired leads to C-to-T transition mutations. Replication errors, despite proofreading, occasionally escape detection.

Induced damage results from environmental exposures. Ultraviolet light causes adjacent thymine bases to form covalent bonds, creating thymine dimers that block replication and transcription. Ionizing radiation generates reactive oxygen species and can cause single- and double-strand breaks. Chemical mutagens include alkylating agents (which add methyl or other groups to bases), crosslinking agents (which covalently link the two strands), and intercalating agents (which insert between base pairs, causing insertion/deletion mutations). Oxidative stress produces 8-oxoguanine, which mispairs with adenine.

<image>Panel A: Depurination showing adenine-containing nucleotide becoming abasic site (empty space) and deamination with cytosine losing amino group to become uracil with chemical structures. Panel B: Thymine dimer with two adjacent thymines forming cyclobutane ring, UV light shown as wavy arrows. Panel C: Double-strand break with DNA duplex completely broken showing ragged ends. Panel D: Bulky adduct (benzo[a]pyrene) attached to guanine distorting helix, with damage type labels, causes, and clinical relevance.</image>

DNA Repair Mechanisms

Cells have evolved multiple repair pathways, each specialized for particular types of damage.

Base excision repair (BER) handles small base modifications such as oxidation, deamination, and alkylation products. The pathway begins when a DNA glycosylase recognizes and removes the damaged base by cleaving the glycosidic bond, creating an abasic site. An AP (apurinic/apyrimidinic) endonuclease then cuts the backbone. DNA polymerase beta fills the single-nucleotide gap, and DNA ligase seals the nick. BER is the primary defense against the approximately 10,000 oxidative lesions that occur daily in each cell.

Nucleotide excision repair (NER) removes bulky, helix-distorting lesions such as thymine dimers and chemical adducts. Rather than removing just the damaged base, NER excises a 24-32 nucleotide oligonucleotide segment containing the lesion. The process involves damage recognition, dual incisions on either side of the lesion (by XPF-ERCC1 and XPG endonucleases), removal of the damage-containing oligonucleotide, gap filling by DNA polymerase, and ligation. NER is the body's defense against UV-induced DNA damage.

Mismatch repair (MMR) corrects replication errors that escape polymerase proofreading—mismatched base pairs and small insertion/deletion loops. The system must distinguish the newly synthesized (error-containing) strand from the template strand, which in eukaryotes is thought to involve recognition of nicks in the new strand. Key proteins include MSH2 and MLH1. Defects in MMR cause microsatellite instability, a hallmark of Lynch syndrome.

Double-strand breaks are the most dangerous form of DNA damage because they completely disrupt chromosome continuity. Two major pathways repair these breaks. Non-homologous end joining (NHEJ) directly ligates the broken ends together, using proteins including Ku70/80 and DNA ligase IV. This pathway is fast but error-prone, often causing small deletions at the junction. It operates throughout the cell cycle. Homologous recombination (HR) uses the sister chromatid as a template to faithfully restore the original sequence. Key proteins include BRCA1, BRCA2, and RAD51. HR is error-free but only available in S and G2 phases when a sister chromatid exists.

<image>Panel A: Base Excision Repair showing 8-oxoG recognized by glycosylase, AP site creation, AP endonuclease cut, Pol beta fill, and ligase seal. Panel B: Nucleotide Excision Repair with thymine dimer causing helix distortion, XPC recognition, XPF/XPG dual incisions creating 24-32 nt gap. Panel C: Mismatch Repair showing G-T mismatch recognized by MSH2/MSH6, strand discrimination, error excision, and gap filling. Panel D: Double-Strand Break Repair comparing NHEJ (direct joining, fast, error-prone) versus HR (sister chromatid template, error-free, S/G2 only).</image>

Clinical Correlations

Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) results from inherited defects in nucleotide excision repair. Patients cannot repair UV-induced thymine dimers, causing extreme sensitivity to sunlight. Even minimal sun exposure causes severe burning, freckling, and skin atrophy. The skin cancer risk is approximately 10,000-fold elevated, with patients developing multiple basal cell carcinomas, squamous cell carcinomas, and melanomas, often in childhood. Some XP forms also involve neurological degeneration, possibly reflecting an inability to repair oxidative damage in neurons. Treatment focuses on rigorous sun protection—patients often become nocturnal to avoid sunlight entirely.

Lynch Syndrome

Lynch syndrome (formerly hereditary non-polyposis colorectal cancer, HNPCC) results from germline mutations in mismatch repair genes, most commonly MLH1 and MSH2. The resulting defective repair causes microsatellite instability—alterations in the length of repetitive DNA sequences—which serves as a diagnostic marker. Patients face approximately 80% lifetime risk of colorectal cancer, 40-60% risk of endometrial cancer, and elevated risks of ovarian, gastric, urinary tract, and other cancers. Unlike familial adenomatous polyposis, Lynch syndrome patients typically develop fewer polyps, but those that arise progress to cancer rapidly. Surveillance with early and frequent colonoscopies, along with consideration of prophylactic surgery, can significantly reduce mortality.

BRCA1/BRCA2 Mutations

BRCA1 and BRCA2 are essential for homologous recombination repair of double-strand breaks. Women carrying germline mutations in these genes face 45-65% lifetime risk of breast cancer and 10-40% risk of ovarian cancer; male carriers have elevated prostate and breast cancer risk. The therapeutic paradigm of synthetic lethality has emerged from understanding these pathways: cells lacking BRCA function become entirely dependent on backup repair pathways involving PARP enzymes. PARP inhibitors (olaparib, niraparib, rucaparib) block this backup pathway, selectively killing BRCA-deficient cancer cells while sparing normal cells that retain at least one functional BRCA copy. This represents a triumph of translating molecular understanding into targeted therapy.

Ataxia Telangiectasia

Ataxia telangiectasia results from mutations in ATM, a kinase central to the cellular response to double-strand breaks. ATM normally senses DNA damage and activates checkpoint pathways that halt cell cycle progression and initiate repair. Patients develop progressive cerebellar ataxia (difficulty with coordination and balance), telangiectasias (dilated blood vessels visible in the eyes and skin), immunodeficiency with recurrent infections, extreme radiation sensitivity, and cancer predisposition—particularly lymphomas and leukemias. Even diagnostic X-rays must be minimized. The neurodegeneration may result from accumulating DNA damage in post-mitotic neurons that cannot dilute damage through cell division.

Summary

• DNA is a double helix with antiparallel strands held by complementary base pairing (A-T, G-C)
• Replication is semi-conservative, bidirectional, and semi-discontinuous
• Key enzymes: helicase, primase, DNA polymerase, ligase, topoisomerase
• Leading strand synthesized continuously; lagging strand as Okazaki fragments
• Telomerase maintains chromosome ends in germ and cancer cells
• Multiple repair pathways correct different types of DNA damage
• Defects in replication/repair cause cancer predisposition and aging syndromes

Key Terms

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