Telomere shortening in humans can induce replicative senescence, which blocks cell division. Cancer cells avoid replicative senescence to become immortal. Two replicative polymerases synthesize DNA in opposite orientations. Strand binding proteins are removed by replicative polymerases. Telomeric double stranded breaks or telomeric dysfunction is generated by exogenous agents or replicative stress. This process is known as "replicative senescence", or the Hayflick limit. The second base pair mutation affects the polymerase which influences replicative capacity. To initiate DNA replication, multiple replicative proteins assemble on and dissociate from these replicative origins. Hence retrotransposons can be thought of as replicative, whereas DNA transposons are non-replicative. These mice suffer high levels of replicative stress and DNA damage. Significantly, the expanded gene families were only previously known to exhibit replicative behaviour within vertebrates. The G phase describes a cellular state outside of the replicative cell cycle.