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Autonomously replicating sequence
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<p>An autonomously replicating sequence (ARS) contains the <a href="/facts/Origin_of_replication/StuSWefk">origin of replication</a> in the <a href="/facts/Yeast/eGD24nfI">yeast</a> <a href="/facts/Genome/31Sm08JT">genome</a>. It contains four regions (A, B1, B2, and B3), named in order of their effect on <a href="/facts/Plasmid/yf59JVlA">plasmid</a> stability. The A-Domain is highly conserved, any mutation abolishes origin function. Mutations on B1, B2, and B3 will diminish, but not prevent functioning of the origin. </p><p>Element A is highly conserved, consisting of the consensus sequence: </p> <p>5'- T/A T T T A Y R T T T T/A -3'</p> <p>(where <i>Y</i> is either <a href="/facts/Pyrimidine/uFRSB8Cq">pyrimidine</a> and <i>R</i> is either <a href="/facts/Purine/9ogLp0Wc">purine</a>). When this element is mutated, the ARS loses all activity. </p><p>As seen above the ARS are considerably A-T rich which makes it easy for replicative proteins to disrupt the H-bonding in that area. ORC protein complex (<a href="/facts/Origin_recognition_complex/kf2zd7FI">origin recognition complex</a>) is bound at the ARS throughout the <a href="/facts/Cell_cycle/nLMT7K4r">cell cycle</a>, allowing replicative proteins access to the ARS. </p><p>Mutational analysis for the yeast ARS elements have shown that any mutation in the B1, B2 and B3 regions result in a reduction of function of the ARS element. A mutation in the A region results in a complete loss of function. </p><p>Melting of DNA occurs within domain B2, induced by attachment of ARS binding factor 1 to B3. A1 and B1 domain binds with origin recognition complex. </p><p>To identify these sequences, yeast mutants unable to synthesize <a href="/facts/Histidine/le7781NF">histidine</a> were transformed with plasmids containing the His gene and random fragments of the yeast genome. If the genome fragment contained an origin of replication, cells were able to grow in a medium lacking histidine. These sequences were termed autonomously replicating sequences, because they were replicated and inherited by progeny without integrating into the host <a href="/facts/Chromosome/FRGf11FC">chromosome</a>. </p>