MCB 121 S2025 Lecture 16: DNA damage, aging and cancer

Vocabulary flashcards based on lecture notes covering DNA damage, aging, and cancer.

DNA damage

Harm to DNA caused by endogenous sources like reactive oxygen species (ROS) or exogenous agents such as UV light, chemotherapeutics, and ionizing radiation.

Reactive oxygen species (ROS)

Byproducts of normal cellular metabolism, mainly from mitochondria, that can damage DNA, proteins, and lipids.

Double-strand breaks (DSBs)

Severe DNA lesions where both strands of the DNA helix are broken, often caused by ionizing radiation or stalled replication forks.

Mismatch repair (MMR)

A DNA repair pathway that corrects replication errors; defects are linked to colorectal cancer and Lynch syndrome.

BRCA1 and BRCA2

Tumor suppressor genes essential for homologous recombination repair of double-strand DNA breaks; mutations increase breast cancer risk.

Homologous recombination (HR)

A high-fidelity DNA repair mechanism that fixes double-strand breaks using a homologous DNA template.

Homology-directed repair (HDR)

The process of repairing DNA double-strand breaks through end resection and strand invasion, mediated by BRCA1 and BRCA2.

RAD51

A protein loaded by BRCA2 onto single-stranded DNA during HR to facilitate strand invasion.

PARP inhibitors

Drugs that inhibit poly(ADP-ribose) polymerase, blocking repair of single-strand breaks and selectively killing BRCA-deficient cancer cells.

Oncogene

A gene that, when mutated or overexpressed, drives uncontrolled cell division and cancer; the normal form is called a protooncogene.

Tumor suppressor genes (TS genes)

Genes that prevent cancer by repairing DNA, regulating cell cycle, and inducing apoptosis; both alleles usually need to be inactivated ('two-hit hypothesis').

Apoptosis

Programmed cell death that removes damaged or dangerous cells.

Telomerase

An enzyme that extends telomeres, often activated in metastatic cancers to maintain chromosome ends during rapid cell division.

Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer, HNPCC)

An inherited cancer syndrome caused by mutations in MMR genes, leading to increased colorectal and endometrial cancer risk.

Loss of heterozygosity (LOH)

The loss of the normal allele in a cell already carrying a mutated allele, commonly via homologous recombination or chromosome missegregation.

Aneuploidy

An abnormal number of chromosomes in a cell, often resulting from chromosome missegregation.

Epigenetic silencing

The repression of gene expression through chromatin modifications or DNA methylation without changing the DNA sequence.

Shelterin complex

A protein complex that protects telomeres from being recognized as DNA breaks.

Non-homologous end joining (NHEJ)

A DNA repair process that joins broken DNA ends without a homologous template, often causing chromosome fusions.

Anaphase bridge

A structure formed when fused chromosomes fail to separate properly during cell division, leading to chromosome breakage.

Bridge-breakage-fusion (BBF) cycles

Repeated cycles of chromosome fusion and breakage causing genomic instability and cancer progression.

Senescence

A stable state of cell cycle arrest that prevents damaged cells from dividing, maintained by pathways involving p53/p21 and p16/pRB.

Crisis

A stage characterized by extensive genomic instability due to telomere dysfunction and chromosome fusion, before telomerase reactivation.

Spectral karyotype

A method using fluorescent probes to visualize chromosomes in different colors, useful for detecting chromosomal abnormalities in cancer cells.

Mosaic loss of Y

The age-related loss of the Y chromosome in some cells of men, associated with shorter lifespan and disease risk.

CpG methylation

Addition of methyl groups to cytosine bases in CpG dinucleotides, an epigenetic mark important for gene regulation.

LINEs and SINEs

Long and short interspersed nuclear elements, repetitive DNA sequences that can transpose and cause genome instability.

Genome-wide association studies (GWAS)

Studies that identify genetic variants correlated with diseases or traits across the genome.

TERT

The catalytic subunit of telomerase.

ANRIL

A long noncoding RNA (lncRNA) antisense to CDKN2A/B, involved in epigenetic regulation and acting as a miRNA sponge.

miRNA sponge

A molecule that binds and sequesters microRNAs, preventing them from repressing their target mRNAs.

Alu elements

Short repetitive DNA sequences embedded in some lncRNAs like ANRIL that facilitate miRNA binding. Also act as retrotransposons (SINE) that function with LINE-1 encoded proteins

Barr body

The inactive X chromosome in XX cells (or XXY) cells, which can become partially reactivated with aging.

XIST

A lncRNA that mediates X chromosome inactivation by recruiting silencing complexes and modifying chromatin.

ATAC-seq

A technique to assess chromatin accessibility by probing open chromatin regions.

Lamin A

A nuclear envelope protein that supports nuclear shape and chromatin organization.

Hutchinson-Gilford progeria syndrome (HGPS)

A premature aging disease caused by a mutation in Lamin A leading to progerin accumulation and nuclear defects.

Progerin

A mutant, farnesylated form of Lamin A that causes nuclear blebbing and premature aging phenotypes.

Epigenetic homeostasis

The balance of epigenetic marks maintaining stable gene expression.

Gompertz Law

A mathematical model describing the exponential increase in mortality with age.

Naked mole rat (NMR)

A long-lived rodent species that defies Gompertz law, showing cancer resistance and longevity traits.

Chromothripsis

A catastrophic genomic event in which a missegregated chromosome is left behind during cell division and becomes trapped in a micronucleus in the cytoplasm.