DNA Replication and Repair Flashcards

A set of vocabulary flashcards derived from the lecture on DNA replication, chromatin structure, DNA repair mechanisms, and associated clinical syndromes.

Nucleoside

A molecule composed of a nitrogenous base and a sugar (base + sugar).

Nucleotide

The building block of DNA consisting of a nitrogenous base, a sugar, and a phosphate group (base + sugar + phosphate).

Purine Bases

A category of nitrogenous bases that includes Adenine and Guanine.

Pyrimidine Bases

A category of nitrogenous bases that includes Cytosine and Thymine.

DNA Double Helix Charge

DNA is negatively charged at a ${pH = 7}$.

Chromatin

A complex found in the nucleus consisting of DNA, histone proteins, and non-histone proteins in an approximate mass ratio of ${1/3:1/3:1/3}$.

Core Histones

Highly conserved basic proteins including ${H2A}$, ${H2B}$, ${H3}$, and ${H4}$ found in a ${1:1:1:1}$ ratio within the nucleosome core.

Linker Histone

The histone known as ${H1}$ which exists in a variable ratio within chromatin structure.

Epigenetics

The study of gene activity control without changing the DNA sequence, primarily achieved through histone tail modifications and DNA methylation.

Euchromatin

A less condensed, gene-rich form of chromatin that is transcriptionally proficient and enriched in acetylated histones.

Heterochromatin

Highly condensed chromatin composed of repetitive sequences (centromeres and telomeres) that is transcriptionally deficient and enriched in methylated DNA and histones.

MeCP2

A protein that binds methylated DNA to regulate chromatin structure and gene expression; it is the primary factor implicated in Rett Syndrome.

Rett Syndrome

A neurodevelopmental disorder characterized by regression, microcephaly, stereotypic hand movements, and seizures, caused by mutations in the ${MECP2}$ gene.

Meier-Gorlin Syndrome

A rare autosomal recessive form of dwarfism caused by mutations in pre-replication complex genes such as ${ORC1, ORC4, ORC6, CDT1, CDC45, GINS, }$ and ${CDC6}$.

Origin Recognition Complex (ORC)

A complex that occupies the replication origin (${Ori}$) throughout the cell cycle to facilitate the initiation of DNA replication.

DNA Polymerase { \text{\alpha} }-primase

The enzyme complex that initiates DNA synthesis by creating a short RNA primer (approximately ${10}$ nucleotides) followed by a short DNA segment (approximately ${20}$ nucleotides).

DNA Polymerase { \text{\delta} }

The enzyme responsible for lagging strand DNA synthesis and the elongation and maturation of Okazaki fragments.

DNA Polymerase { \text{\epsilon} }

The enzyme responsible for replisome assembly and leading strand DNA synthesis.

PCNA

The Proliferating Cell Nuclear Antigen, or 'sliding clamp,' which is a ring-shaped factor recruited to increase the processivity (stability) of DNA polymerases.

RPA

A protein that binds to and stabilizes single-stranded DNA (${ssDNA}$) during the replication process.

Topoisomerases

Enzymes that resolve DNA supercoiling caused by unwinding; Type I cuts one strand, while Type II cuts both strands to allow rotation and re-ligation.

Telomerase

A telomere-specific reverse transcriptase consisting of a catalytic subunit (${TERT}$) and an RNA template (${TERC}$); it is active in stem cells and ${90\%}$ of human cancers.

Dyskeratosis Congenita (DKC)

A disorder caused by telomerase defects, characterized by the clinical triad of dystrophic nails, patchy skin hyper-pigmentation, and oral leukoplakia.

Base Excision Repair (BER)

A repair mechanism that corrects damaged bases (e.g., from depurination or deamination) using DNA glycosylases to evaluate and remove altered bases.

Nucleotide Excision Repair (NER)

A repair pathway that removes 'bulky' lesions, such as UV-induced pyrimidine dimers, by scanning for distortions in the DNA double helix.

Mismatch Repair (MMR)

A mechanism that corrects mismatched base pairs using ${MutS}$ and ${MutL}$ proteins, identifying the incorrect strand by the orientation of the sliding clamp.

Non-homologous End Joining (NHEJ)

An error-prone mechanism for repairing double-stranded DNA breaks that results in the loss of nucleotides at the repair site and occurs throughout the cell cycle (primarily ${G1}$).

Homologous Recombination (HR)

An error-free mechanism for repairing double-stranded DNA breaks that uses an undamaged homologous DNA molecule as a template, occurring primarily in ${S}$ and ${G2}$ phases.

Xeroderma Pigmentosum (XP)

A condition caused by mutations in Nucleotide Excision Repair (NER) factors, resulting in extreme solar sensitivity and a ${2,000}$-fold increased risk of skin cancer.

Lynch Syndrome

An autosomal dominant disorder caused by mutations in DNA mismatch repair (MMR) genes (e.g., ${MSH2, MLH1}$), leading to early-onset colorectal and endometrial cancers.

Li-Fraumeni Syndrome (LFS)

An autosomal dominant condition caused by germline mutations in the ${p53}$ tumor suppressor gene, resulting in a nearly ${100\%}$ lifetime cancer risk for females.

Ataxia Telangiectasia (AT)

An autosomal recessive disorder caused by mutations in the ${ATM}$ gene, characterized by uncoordinated movement, dilated blood vessels, immune deficiency, and hypersensitivity to ionizing radiation.