Translesion DNA Synthesis

• Cells bypass lesions encountered at the replication fork during DNA synthesis and correct them after replication is finished

• Enzymes used in this mechanism can correctly synthesize new strand in spite of lesion on template DNA

Recombinational Repair

• Uses recombination with undamaged DNA molecule to repair damaged DNA

• Often used to fix damage found in DNA replication

• One strand of parent DNA needs to have been undamaged and copied during replication to provide normal daughter molecule for repair of damaged strand

• Provides repair mechanism for DS breaks from chemicals and ionizing radiation

Genetic Recombination• Important mechanism in DNA repair and increasing

genetic diversity• Allows for re-assortment of genes into different

combinations• Can be initiated by DS breaks in the DNA• Occurs between DNA molecules that share sequence

homology over hundreds of bases• Doesn’t alter overall arrangement of genes on a

chromosome• Results from breakage and rejoining of two parental

molecules with different combination from the original– Complementary strands base pair to each other– Overlapping SS sections are exchanged during formation of heteroduplex

in the Holliday model– Heteroduplex separates and recombined regions are on new

chromosomes– Facilitated by enzymes

DNA Rearrangement

• Recombinational events that lead to rearrangements in genomic DNA

• Some function in controlling gene expression in some cell types, others have role in evolution by contributing to genetic diversity

• First found genes that moved to other locations in genome to alter expression of nearby genes in corn in the 1940s– Idea not widely accepted until 1970s

• Transposable elements (transposons) first identified in bacteria, make up large part of higher eukaryote genomes

DNA Rearrangements

• Site-specific recombination occurs between specific DNA sequences homologous over short stretches of DNA– Proteins recognize target DNA sequences,

leads to programmed DNA rearrangement with roles in development and regulation of gene expression

– Process used in vertebrate immunoglobulin genes

DNA Rearrangements

• Transposition by DNA intermediates occurs when DNA sequences move to another area in genome and have no requirement for sequence homology– Transposons move this way

• Insertion sequences move from one chromosome site without copying DNA

• Other transposons move by replicative mechanism where DNA is copied and the copy is inserted elsewhere

DNA Rearrangements

• Transposition by RNA intermediate occurs when DNA is transcribed to RNA then reverse transcribed to DNA for insertion– Retrotransposons are transposable elements that

move via reverse transcription of an RNA intermediate

– Retroviruses contain RNA genomes in their virus particles but replicate by the synthesis of a DNA provirus• Reverse transcriptase is a DNA polymerase that uses an

RNA template and a primer to synthesize DNA

– Because of the way it functions, direct repeats of hundreds of nucleotides called LTRs are created at each end of the DNA

DNA Rearrangements

• Other retrotransposons use RNA intermediates but are not packaged into viral particles for infection of new cells– They only move within host cell’s genome– Retrovirus-like elements or LTR retrotransposons are

like retroviruses but do not produce infectious particles

– Non-LTR retrotransposons lack LTRs but still transpose by RNA intermediate

– Other sequences elements transpose by RNA intermediate but don’t code for reverse transcriptase

Gene Amplification

• Increases copy number of genes in cells• Result of repeated rounds of DNA replication• Found as free extrachromosomal molecules or

tandem arrays of sequences within a chromosome

• Results in increased expression of amplified gene

• Sometimes developmentally programmed to support cells

• Abnormal occurrence is associated with cancers

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