Molecular Genetics

ARS can function as origins of replication but do not always do so.

Facts

• A copy of ARS1, an early-firing origin of Saccharomyces cervisiae, was inserted by recombinant DNA techniques near the late firing origin ARS501 of S. cerevisiae chromosome V. A derivative of the resulting strain had the ARS 501 sequence deleted and, along with the wild type, served as single-origin controls.
• Origin behavior was studied by two-dimensional gel electrophoresis. Both ARS1 and ARS501 fired late during replication.
• The presence of ARS1 reduced firing of ARS501. The presence of ARS501 reduced the firing of ARS1. Both origins were rarely, if at all, active on the same chromosome at the same time.

Interpretations

• The context of an ARS origin determines whether it fires early or late during replication.
• Firing of one origin inhibits the firing of another in its immediate vicinity.
• When multiple origins exist in close proximity, random processes decide from which origin the chromosome segment will be replicated. Thus, some chromosome stretches may appear to initiate replication randomly (ref).

Further information

• The firing of origins must be coordinated with the cell cycle so that no origin fires more than once during each cycle.
• The inhibition of origin firing by the proximity of an active origin has also been noted in mammalian cells (ref).
• Cyclin proteins play important roles in this coordination.
• Endoreduplication results when this coordination is by-passed.
• A different mechanism is used to regulate replication initiation in E. coli.
• Regulation of ColE1 plasmid replication involves RNA molecules.