The roles of DNA(cytosine-5) methyltransferase1 in carcinogenesis related to cellular factors, virus and chemicals

Infection with HPV-16 genomes which is a primary cause of cervical cancer was shown to be targeted in-vivo by CpG methylation. In a clinical study it was discovered that genomic hypomethylation of the LCR and promoter region correlated with carcinogenic progression. The HPV-16 genome could be demethylated using 5AzadC and MMS which led to the over-expression of the late genes, hence suppressing the early genes. DNMT1 and PCNA was found to interact with two distinct regions of Hsp70. The binding site of Hsp70 was localized to the N-terminal of DNMT1. The disruption of this site in DNMT1b abolished its interaction with Hsp70. Activation of the ATPase activity of Hsp70 by PCNA could play a role in the binding to DNMT1 and hence protecting the complex from attack by p21Waf1/Cip1.

Author dc:creator

• VINAY BADAL

• DNMT1, DNA methylation, HPV-16, cervical cancer, PCNA, Hsp70