Aberrant S-Phase induction is the premature and prolonged entry into the S-Phase of the cell cycle caused by malfunction at the G1/S cell-cycle checkpoint.
Cell-cycle regulation is controlled by a number of essential proteins that insure DNA integrity prior to replication, the separation of duplicated chromosomes and final cell division. Endogenous and exogenous factors that interfere with the normal activity of these proteins result in malfunction of the cell-cycle.
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The Cell Cycle
Cell reproduction, including the replication of DNA followed by division of the nucleus and partitioning of the cytoplasm to yield two identical daughter cells, is carefully controlled through a sequential process known as the cell-cycle.
The cell-cycle includes four discrete phases:
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- In S-Phase, DNA is replicated in the nucleus and chromosomes are duplicated.
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- In M-Phase, cell division occurs, generating two equal daughter cells.
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Cell-cycle Checkpoints
Cell-cycle checkpoints G1/S and G2/M actively halt progression through the cell-cycle until earlier processes, including DNA synthesis and mitosis, are complete.
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- At the G1/S checkpoint, the DNA is checked for any mistakes and these are corrected prior to the replication of the DNA.
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- At the G2/M checkpoint, the duplicated chromosomes are checked for any mistakes prior to chromosome separation and cell division.
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- Failure to repair DNA mistakes and chromosome mistakes results in the generation and accumulation of DNA defects that are passed on to the daughter cells leading to the generation of abnormal cells.
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| Specific genes required for DNA replication are induced and over-expressed in aberrant S-Phase induction. |
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Aberrant S-Phase Induction
Cell-cycle regulation is controlled by a number of essential proteins that ensure DNA integrity prior to replication, the separation of duplicated chromosomes and final cell division. Following persistent high-risk HPV infection, the HPV oncoproteins E6 and E7 are implicated in a number of cellular processes related to increased proliferation and neoplastic transformation of the infected keratinocytes. E6 abrogates cell cycle checkpoints at the G1/S and G2/M boundaries, while E7 promotes acceleration into S-Phase, with prolonged expression of the S-Phase genes required for DNA replication, resulting in aberrant S-Phase induction. In cells positive for aberrant S-Phase induction, a number of proteins are over expressed, including MCM2 and TOP2A. |
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Malfunction at the G1/S cell-cycle checkpoint, induced by E6 and E7 oncoproteins, results in premature and prolonged entry into the S-Phase, a process known as aberrant S-Phase induction.
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