A representation of the DNA damage-induced cell cycle checkpoint pathway in mammalian cells. DNA damage results in accumulation of the p53 protein. Accumulation.

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A representation of the DNA damage-induced cell cycle checkpoint pathway in mammalian cells. DNA damage results in accumulation of the p53 protein. Accumulation of wtp53 increases levels of p21waf1/cip1, which in turn inhibits activation of cyclin-cdk complexes. pRB therefore remains in the unphosphorylated (active) state, and pRB-associated E2F transcription factors are unable to activate transcription of genes required for progression from G1 into S phase. Consequently, cells arrest in late G1. High-risk HPVs can disrupt the pathway at multiple points: through interaction of E6 with p53 and, further downstream, through the effects of E7 on pRB, p21, and the G1 cyclins. (Modified with permission from Alani and Münger K: Human papillomaviruses and associated malignancies. J Clin Oncol 16:330-337, 1998.) Source: Cervical Cancer, The Online Metabolic and Molecular Bases of Inherited Disease Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: https://ommbid.mhmedical.com/DownloadImage.aspx?image=/data/books/971/ch53fg2.png&sec=62668980&BookID=971&ChapterSecID=62668955&imagename=&gboscontainerID=0 Accessed: October 28, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved