Genomic Elements and DNA Repair Mechanisms in Eukaryotes and Prokaryotes

Introns early model

Genes originated interrupted, aiding exon shuffling for domain recombination.

Introns late model

Early genes continuous, introns added later.

Exon shuffling

Recombination mixes exons for new proteins; mobile introns insert.

Pseudogenes

Inactivated gene copies; processed (from cDNA integration), nonprocessed (duplication + mutation).

New gene function

Arises from duplication divergence, pseudogene repurposing (e.g., regulation).

Transposons

>50% human DNA, proliferate checked by selection; enable shuffling, regulatory roles, genome size increase.

Mismatch repair (MMR)

Fixes mispaired bases, usually right after replication; preferentially repairs the newly made daughter strand.

Photoreactivation

A light-dependent repair system that directly splits UV-induced pyrimidine dimers; described as nonmutagenic.

Direct reversal

Alkylation damage can be reversed by methyltransferase enzymes in a suicide reaction.

Excision repair

Removes damaged DNA from one strand and resynthesizes the missing stretch using the opposite strand as template.

Base excision repair (BER)

Repairs single-base damage such as deamination or alkylation; requires glycosylases that remove damaged bases.

Nucleotide excision repair (NER)

Repairs bulky lesions such as UV-induced pyrimidine dimers; has two subpathways: global genome repair and transcription-coupled repair.

Prokaryotic excision repair

In E. coli, makes incisions on both sides of damage, removes the damaged segment, and replaces it by new synthesis.

Recombination-repair

Uses recombination to replace a damaged region, especially when replication leaves a gap opposite a damaged template.

Double-strand break repair

In eukaryotes, RAD52 group, MRX/MRN complex, and Rad51 help process broken ends and invade the intact template for repair.

Nonhomologous end joining (NHEJ)

Repairs double-strand breaks when a homologous template is not available; can ligate blunt DNA ends.

SOS response in prokaryotes

DNA damage activates RecA, which promotes LexA autocleavage and induces many repair genes.

Error-prone repair

Occurs when damaged DNA has not been repaired and the normal replicative polymerase stalls; DNA polymerase V or IV can synthesize across the lesion.

Translesion synthesis

The process where DNA made by error-prone polymerases often contains errors.

MMR usage

Used immediately after replication to fix replication mismatches and insertion/deletion-type errors.

Photoreactivation and NER usage

Used after UV damage, especially when pyrimidine dimers form.

BER usage

Used for single-base lesions such as deamination, depurination, and alkylation-related damage.

Direct reversal usage

Used for alkylation damage.

Recombination-repair usage

Used when replication encounters damage and leaves a gap in the newly synthesized strand.

Fork recovery systems

Used when a replication fork stalls at damaged DNA or a nick.

Homologous recombination or NHEJ usage

Used when there is a double-strand break; NHEJ is used specifically when homologous sequence is not available.

Transcription-coupled NER

Used when damage is present in the transcribed strand of active genes.

Global genome repair

Surveys damage throughout the genome.

Double-strand breaks (DSBs)

Serious lesions repaired either by homologous recombination or NHEJ.

Role of homologous chromosomes

Provides the undamaged template needed for accurate recombination-based repair.

Chromatin in repair systems

Repair happens in chromatin; histone modification and chromatin remodeling are essential for efficient repair.

γ-H2AX

A DSB-dependent histone modification that helps recruit chromatin-modifying activities and assemble repair factors at the break.