Description

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Context

Extrachromosomal DNA (ecDNA) has emerged as a significant player in cancer biology challenging long-held genetic principles.

Once dismissed as a rare occurrence, ecDNA is now recognized for its role in cancer progression, metastasis and drug resistance. Recent studies led by the eDyNAmiC team have shed light on its formation, function and implications in oncology.

About ecDNA

In normal cells, DNA resides in 23 pairs of chromosomes within the nucleus. However, processes like DNA damage or errors during cell replication can result in fragments of DNA breaking away to form circular structures known as ecDNA.

First identified 50 years ago, ecDNA was initially deemed irrelevant due to its presence in only 1.4% of tumors.

Modern genomic techniques revealed its prevalence in nearly 40% of cancer cell lines and up to 90% of certain tumor types highlighting its critical role.

Characteristics:

Contains multiple copies of oncogenes (genes capable of causing cancer).

Freely moves within the nucleus forming hubs where oncogene expression is amplified.

Formation Triggers:

Environmental factors: Smoking, chemical exposure.

Genetic mutations: Linked to chromothripsis, a process where chromosomes break and rearrange.

Role in Cancer Growth:

ecDNA often carries oncogenes enhancing their expression beyond what is possible with chromosomal DNA. Oncogenes are a group of genetic mutations that may cause cancer. They're a mutated form of genes that manage cell growth. When these genes change into oncogenes, they cause cells to grow and divide uncontrollably. Oncogenes are powerful.

The dynamic nature of ecDNA accelerates tumor evolution aiding cancer cells in resisting treatments.

ecDNA interacts with other ecDNA forming zones where oncogenes are overexpressed. This contributes to aggressive tumor behavior.

ecDNA and Genetic Laws

Violation of Mendel’s Law:

Mendel’s third law posits that genes on different chromosomes are inherited independently. ecDNA, however, is passed on in clusters during cell division preserving specific oncogene combinations—a phenomenon termed the “jackpot effect.”

This discovery redefines gene inheritance patterns. Coordinated segregation of ecDNA during cell division boosts cancer cell survival and adaptability.

DNA: Structure, Types, and Replication

Aspect	Details
Definition	DNA (Deoxyribonucleic Acid) is a molecule that carries the genetic instructions essential for the growth, development, functioning and reproduction of all living organisms.
Structure
Composition	DNA consists of nucleotides each containing a deoxyribose sugar, a phosphate group and one of four nitrogenous bases (Adenine, Thymine, Cytosine, Guanine).
Double Helix	DNA is structured as a double-stranded helix with two strands running in opposite directions (antiparallel) and connected by complementary base pairing (A-T, C-G).
Backbone	The sugar-phosphate backbone provides structural stability.
Types
A-DNA	Right-handed helix, dehydrated form of DNA found under low-humidity conditions.
B-DNA	Most common form in cells right-handed helix with 10.5 base pairs per turn.
Z-DNA	Left-handed helix occurs in regions with high GC content or during transcriptional activity.
Replication
Semi-Conservative	DNA replication is semi-conservative; each daughter DNA molecule contains one parent strand and one newly synthesized strand.
*Step 1. Initiation*	Begins at the origin of replication, with the enzyme helicase unwinding the DNA helix to form a replication fork.
*Step 2. Elongation*	DNA polymerase synthesizes new DNA strands complementary to the parent strands. The leading strand is synthesized continuously while the lagging strand forms Okazaki fragments.
*Step 3. Termination*	DNA synthesis ends when replication forks meet and ligase seals any gaps in the newly formed DNA strands.
Enzymes Involved	Helicase, DNA polymerase, primase, ligase and topoisomerase are key enzymes.

Sources:

HINDU

PRACTICE QUESTION

Q.How does extrachromosomal DNA (ecDNA) challenge traditional genetic principles and what implications does it have for cancer biology and treatment? (150 Words)