Chapter 23 - Cancer

Human cells

________ contain a battery of glycosylases, each of which is specific for a different set of chemically modified DNA bases.

Depurination

________ occurs spontaneously and is fairly common in mammals.

Environmental chemicals

________ were originally associated with cancer through experimental studies in animals.

Mitogen withdrawal

________ prior to passage through the restriction point leads to the accumulation of p16.

Virus

________ encoded proteins can bind and activate host cell receptors which cause proliferation.

Mdm2

The activity of p53 normally is kept low by a protein called ________.

Telomeres

________ provide the solution to the end- replication problem- the inability of DNA polymerases to completely replicate the end of a double- stranded DNA molecule.

Cells

________ have other repair systems for preventing mutations due to copying errors and exposure to carcinogens.

Positive

________- and negative- acting proteins precisely control the entry of cells into and their progression through the cell cycle, which consists of four main phases: G1, S, G2, and mitosis.

nonfunctional 235

Cells with abnormal numbers of chromosomes form when certain cell- cycle checkpoints are ________- The Role of Carcinogens and DNA Repair in Cancer.

DNA

The complete phosphorylation of Rb irreversibly commits the cell to ________ synthesis.

Cancer

________ can be caused by slow- acting retroviruses by integrating near a proto- oncogene.

Angiogenesis

________ is needed to grow into a large mass by both primary and secondary tumors 23.2: The Genetic Basis of Cancer.

RB

________ is the first tumor suppressor gene to be recognized 23.3: Oncogenic Mutations in Growth Promoting Proteins.

AP

The segment of the damaged strand containing the baseless deoxyribose is excised by a(n) ________ endonuclease that cuts the DNA strand near the abasic site.

Transcription factors

________ such as Fos, Jun, and Myc being produced unneeded can cause the transformation to occur sooner than needed 23.4- Mutations Causing Loss of Growth- Inhibiting and Cell- Cycle Control.

Chk2

Under stressful conditions, the ATM kinase also phosphorylates and thus activates ________, a protein kinase that phosphorylates the protein phosphatase Cdc25A, marking it for ubiquitin- mediated destruction.

complex mechanisms

The ________ for regulating the eukaryotic cell cycle are prime targets for oncogenic mutations.

Chemical carcinogens

________ are believed to be risk factors for many human cancers, a direct linkage to specific cancers has been established only in a few cases (the most important being lung cancer)

3n5

Proofreading depends on the ________ exonuclease activity of some DNA polymerases.

point mutation

A missense ________ in one of the two p53 alleles in a cell can abrogate almost all p53 activity because virtually all the oligomers will contain at least one defective subunit, and such oligomers can not function as a transcription factor.

growth promoting

They multiply when there is an absence of any ________ factors needed for the proliferation of cells.

homologous recombination

At one time ________ was thought to be a minor repair process in human cells.

normal development

During ________, many cells are designated for programmed cell death, also known as apoptosis.

nucleotide excision

Cells use ________ repair to fix DNA regions containing chemically modified bases, often called chemical adducts, that distort the normal shape of DNA locally.

p53 protein

The ________ is a sensor essential for the checkpoint control that arrests cells with damaged DNA in G1.

CLL tumours

________ are therefore attributable to a failure of cell death.

G residues

After chemical modification by liver enzymes, aflatoxin becomes linked to ________ in DNA and induces G- to- T transversions Loss of High- Fidelity DNA Excision- Repair Systems Can Lead to Cancer.

proper DNA repair

Without ________, people with xeroderma pigmentosum or hereditary nonpolyposis colorectal cancer have a propensity to accumulate mutations in many other genes.

human papillomavirus

The activity of p53 also is inhibited by a(n) ________ (HPV) protein called E6.

cyclin CDK

The proteins that function as ________ inhibitors play an important role in regulating the cell cycle.

Mdm2 gene

The ________ is amplified in many sarcomas and other human tumours that contain a normal p53 gene.

Repair

________ of a double- strand break by homologous recombination involves reactions between three DNA molecules- the two DNA ends and the intact DNA strands from the sister chromatid.

Oncogenes

________ are converted by one of the two alleles in proto- oncogenes when a mutation is activated.

tumor suppressor genes

Mutations can undermine growth control by inactivating ________, but these genes can also be silenced by repressive chromatin structures.

ability of chemical

The ________ and physical carcinogens to induce cancer can be accounted for by the DNA damage that they cause and by the errors introduced into DNA during the cells efforts to repair this damage.

Constitutive receptor activity

________ is caused by mutations or chromosomal translocations that let RTKs grow.

DNA

________ is continually subjected to a barrage of damaging chemical reactions.

Mdm2

When ________ is bound to p53, it inhibits the transcription- activating ability of p53 and catalyzes the addition of ubiquitin molecules, thus targeting p53 for proteasomal degradation.

Cancer

________ is involved in many aspects of molecular cell biology and is an abbreviation in cellular behavior.

DNA

Even if ________ were not exposed to damaging chemicals, ________ is inherently unstable.