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Promoter hypermethylation of homologous recombination genes: Target for therapeutic agents.

Zwarteveen, R.K. (2010) Promoter hypermethylation of homologous recombination genes: Target for therapeutic agents. Bachelor's Thesis, Biology.

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Abstract

Cells are constantly attacked during normal metabolism by agents like oxygen and free radicals which affect the DNA and result in DNA modifications such as single- and double stranded breaks (DSBs), which can ultimately result in DNA mutations. This breakage of the DNA has several negative results like chromosomal aberrations. DSBs are the target for DNA repair mechanisms, non homologous recombination (NHEJ) and homologous recombination (HR). Conservative HR is the error free mechanism where the identical sister chromatid in the late S and G2 phase is used for restoring the same sequence that was present before the break. Several cancers have genetic mutations and/or epigenetic silenced HR genes. Epigenetic silencing is a result of promoter hypermethylation in CpG rich sequences. For instance, there are a great number of studies reporting that the HR gene BRCA1 is silenced in sporadic breast cancer. Other studies report the promoter hypermethylation of the ATM and BRCA2 gene. There are many more genes involved in the HR DNA repair, of which no data of silencing are present yet. Promoter hyper methylation of HR genes could be discovered with the DNA microarray technique and could serve as a biomarker for specific HR deficient cancers and detect cells which are susceptible to cancer. When promoter hypermethylation is present, PARP inhibitors and demethylating agents could be used to treat and prevent these cancers.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:31
Last Modified: 15 Feb 2018 07:31
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/9294

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