Mutations in the tumor suppressor breast cancer susceptibility gene 1
(BRCA1), an important player in the DNA damage response, apoptosis,
cell cycle regulation and transcription, confer a significantly elevated life-time risk for breast and ovarian cancer.
Some limited understanding of self-renewal exists and, intriguingly, implicates gene products that are associated with the chromatin state, a high-order organization of chromosomal DNA that influences transcription. These include members of the polycomb family, a group of zinc finger–containing transcriptional regulators that interact with the chromatin structure, contributing to the accessibility of groups of genes for transcription.
The cell cycle-dependent element (CDE) and the cell cycle genes homology
region (CHR) control the transcription of genes with maximum expression
phase and in mitosis. Promoters of these genes are repressed by pro-teins binding to CDE⁄CHR elements in G0 and G1 phases. Relief from
repression begins in S phase and continues into G2
phase and mitosis.
The finding of a genome-wide oscillation in transcription that gates cells
into S phase and coordinates mitochondrial and metabolic functions
has altered our understanding of how the cell cycle is timed and how stable
cellular phenotypes are maintained.
All cells, from prokaryotes to vertebrates, synthesize enormous amounts of
rRNA to produce 1–2 million ribosomes per cell cycle, which are required
to maintain the protein synthesis capacity of the daughter cells. In recent
years, considerable progress has been made in the elucidation of the basic
principles of transcriptional regulation and the pathways that adapt cellular
rRNA synthesis to metabolic activity, a process that is essential for under
Ribonucleotide reductase is essential for the synthesis of all
four dNTPs required for DNA replication. The enzyme is
composed of two proteins, R1 and R2, which are both
needed for activity. Expression of the R1 andR2mRNAs is
restricted to the S-phase of the cell cycle, but the R1 andR2
promoters shownoobvious sequence homologies that could
indicate coordination of transcription.
In this chapter, students will be able to understand: Chromatin structure is based on successive levels of DNA packing; gene expression can be regulated at any stage, but the key step is transcription; cancer results from genetic changes that affect cell cycle control;...
Retroviral vectors have gained an increasing value in gene therapy because they stably deliver
therapeutic genes to the host cell genome. These therapeutic genes are supposed to rectify
consequences of inherited and acquired mutated genes in the host cell genome, or alter host
cell function to cure diseases.
Type 2A serine⁄threonine phosphatases are part of the PPP subfamily that
is formed by PP2A, PP4 and PP6, and participate in a variety of cellular
processes including transcription, translation, regulation of the cell cycle,
signal transduction and apoptosis.
E2F transcription factors play an important role in the
regulation of cell cycle progression. E2F6, the most recently
identified member of the E2F family, is a retinoblastoma-protein-independent transcriptional repressor that is
required for developmental patterning of the axial skeleton.
It has recently been shown that theE2f6locus produces two
different mRNAs, E2F6 and E2F6b. The E2F6b mRNA
contains an additional exon that is inserted by alternative
Recently, the conserved human LINC⁄DREAM complex has been
described as an important regulator of cell cycle genes. LINC consists of a
core module that dynamically associates with E2F transcription factors,
p130 and the B-MYB transcription factor in a cell cycle-dependent manner.
In this study, we analyzed the evolutionary conserved LIN54 subunit of