Phase Variation - Slipped Strand Mispairing

Slipped Strand Mispairing

Slipped strand mispairing (SSM) is a process that produces mispairing of short repeat sequences between the mother and daughter strand during DNA synthesis. This RecA-independent mechanism can transpire during either DNA replication or DNA repair and can be on the leading or lagging strand. SSM can result in an increase or decrease in the number of short repeat sequences. The short repeat sequences are 1 to 7 nucleotides and can be homogeneous or heterogeneous repetitive DNA sequences.

Altered gene expression is a result of SSM and depending where the increase or decrease of the short repeat sequences occurs in relation to the promoter will either regulate at the level of transcription or translation. The outcome is an ON or OFF phase of a gene or genes.

Transcriptional regulation (bottom portion of figure) occurs in several ways. One possible way is if the repeats are located in the promoter region at the RNA polymerase binding site, -10 and -35 upstream of the gene(s). The opportunistic pathogen H. influenzae has two divergently oriented promoters and fimbriae geneshifA and hifB. The overlapping promoter regions have repeats of the dinucleotide TA in the -10 and -35 sequences. Through SSM the TA repeat region can undergo addition or subtraction of TA dinucleotides which results in the reversible ON phase or OFF phase of transcription of the hifA and hifB. The second way that SSM induces transcriptional regulation is by changing the short repeat sequences located outside the promoter. If there is a change in the short repeat sequence it can affect the binding of a regulatory protein, such as an activator or repressor. It can also lead to differences in post-transcriptional stability of mRNA.

Translation of a protein can be regulated by SSM if the short repeat sequences are in the coding region of the gene (top portion of the figure). Changing the number of repeats in the open reading frame can affect the codon sequence by adding a premature stop codon or by changing the sequence of the protein. This often results in a truncated (in the case of a premature stop codon) and/or nonfunctional protein.

Read more about this topic:  Phase Variation

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