Gene Co-Expression Analysis of Human Reveals Functional Networks Associated with DNA Replication, DNA Damage Response, and Cell Cycle Regulation.

Ribonuclease (RNase) H2 is a key enzyme for the removal of RNA found in DNA-RNA hybrids, playing a fundamental role in biological processes such as DNA replication, telomere maintenance, and DNA damage repair. RNase H2 is a trimer composed of three subunits, being the catalytic subunit. expression levels have been shown to be upregulated in transformed and cancer cells. In this study, we used a bioinformatics approach to identify co-expressed genes in different human tissues to underscore biological processes associated with expression. Our analysis shows functional networks for involvement such as DNA replication and DNA damage response and a novel putative functional network of cell cycle regulation. Further bioinformatics investigation showed increased gene expression in different types of actively cycling cells and tissues, particularly in several cancers, supporting a biological role for but not for the other two subunits of RNase H2 in cell proliferation. Mass spectrometry analysis of -bound proteins identified players functioning in cell cycle regulation. Additional bioinformatic analysis showed that correlates with cancer progression and cell cycle related genes in Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) Pan Cancer datasets and supported our mass spectrometry findings.