ERRORS IN CELL

CYCLE:
RESULTING DISEASES
AND DISORDERS
I. Introduction
The cell can check for any errors during the cell
cycle and often they are fixed, and then the cell
cycle continues. If the cell cannot fix the error, often
the cell will apoptosis (cell suicide). Occasionally
the error is not picked up and the cell will become
mutated.
 Errors in Cell Cycle
(Mitosis and Meiosis)
: Errors in Meiosis
: Errors in Meiosis
Nondisjunction-
•Homologous chromosomes fail to separate during anaphase 1 of meiosis
•Some cells have extra chromosomes and others with missing chromosom
: Errors in Meiosis
Crossing over error – error in crossover formation results in
chromosome nondisjunction leading to aneuploidy, which causes
infertility, miscarriages, birth defects, and cancer.

Chromosomal missegregation - A major consequence of segregation

defects is the change in the relative dosage of products from genes
located on the missegregated chromosomes.
- Chromosome segregation errors during gamete formation in meiosis
are a primary cause of human birth defects and infertility.
.
: Errors in Meiosis
The second stage at which segregation occurs during meiosis is prophase II (see meiosis
diagram). During this stage, segregation occurs by a process similar to that during mitosis,
except that in this case prophase II is not preceded by a round of DNA replication. Thus the
two chromatids comprising each chromosome separate into different nuclei, so that each
nucleus gets a single set of chromatids (now called chromosomes) and each nucleus becomes
included in a haploid gamete (see stages following prophase II in the meiosis diagram).

Meiotic Arrest - Oocytes

are arrested at the first meiotic prophase, held in
meiotic arrest by the surrounding follicle cells until a surge of LH
from the pituitary stimulates the immature oocyte to resume meiosis.
Meiotic arrest depends on a high level of cAMP within the oocyte.

.
 Errors in Cell Cycle
(Mitosis and Meiosis)
: Errors in MITOSIS
: Errors in MITosis
Chromosomal missegregation-. cells may exit mitosis without proper
chromosome segregation and cytokinesis, resulting in the formation of a single
tetraploid cell.
During mitosis chromosome segregation occurs routinely as a step in cell
division (see mitosis diagram). As indicated in the mitosis diagram, mitosis is
preceded by a round of DNA replication, so that each chromosome forms two
copies called chromatids. These chromatids separate to opposite poles, a process
facilitated by a protein complex referred to as cohesin. Upon proper segregation,
a complete set of chromatids ends up in each of two nuclei, and when cell
division is completed, each DNA copy previously referred to as a chromatid is
now called a chromosome.
Chromosomal Fragmentation - a new type of cell death that takes place during
: Errors in MITosis
Chromosomal Fragmentation - a new type of cell death that takes place during
metaphase where condensed chromosomes are progressively degraded.

Chromosome fragmentation represents an efficient means of induced cell death

and is a clinically relevant biomarker of mitotic cell death. Chromosome
fragmentation serves as a method to eliminate genomically unstable cells.
Paradoxically, this process could result in genome aberrations common in
cancer.
: Errors in MITosis
Cytokinesis Failure- As a highly regulated, complex process, Cytokinesis
failure leads to both centrosome amplification and the production of tetraploid
cells, which may set the stage for the development of tumor cells. However,
tetraploid cells are abundant components of some normal tissues including the
liver and heart, indicating that cytokinesis is physiologically regulated.

Spindle Assembly failure - If the spindle fibers failed to form during

mitosis, then the chromosomes would also fail to segregate naturally.
The spindle fibers are involved in the movement and positioning of
chromosomes during cell division.
Cancer and the
Cell Cycle
 Cancer
• A disease of uncontrolled cell division. Its development is usually
linked to a series of changes in the activity of cell cycle regulators.
For example,
• inhibitors of the cell cycle keep cells from dividing when
conditions aren’t right,
• Too little activity of these inhibitors can promote cancer.
• These changes in activity are due to mutations in the genes that
encode cell cycle regulator proteins.
Terms to remember in
errors in the cell cycle
Oncogenes - is a mutated proto-oncogene that has the potential to cause cancer.
Mutations that turn proto-oncogenes into oncogenes can take different forms. Some change
the amino acid sequence of the protein, altering its shape and trapping it in an “always on”
state. Others involve amplification, in which a cell gains extra copies of a gene and thus starts
making too much protein. In still other cases, an error in DNA repair may attach a proto-
oncogene to part of a different gene, producing a “combo” protein with unregulated activity.
Tumor suppressor genes - are segments of DNA that code for negative regulator proteins, a
type of regulator that, when activated, can prevent the cell from undergoing uncontrolled
division.
Negative regulators of the cell cycle may be less active (or even nonfunctional) in cancer
cells. For instance, a protein that halts cell cycle progression in response to DNA damage may
no longer sense damage or trigger a response.
Proto-oncogenes - are genes that
normally help cells grow and divide
to make new cells, or to help cells
stay alive.
- Genes that code for positive cell
cycle regulators.
How do Cancer cells develop?
• Cancer develops when the normal processes that control cell behavior fail, and
a rogue cell becomes the progenitor of a group of cells that share its abnormal
behaviors or capabilities.
• Generally results from an accumulation of genetic damage in cells over time.
When cells grow old or become damaged, they die, and new cells take their
place.
• This orderly process breaks down, and abnormal or damaged cells grow and
multiply when they shouldn’t.
• These cells may form tumors, which are lumps of tissue. Tumors can be
cancerous or not cancerous (benign)
What’s wrong with cancer cells?
 Cancer cells behave differently than normal cells in the body. Many of these
differences are related to cell division behavior.

 For example, cancer cells can multiply in culture (outside of the body in a
dish) without any growth factors, or growth-stimulating protein signals, being
added. This is different from normal cells, which need growth factors to grow
in culture.

 .Cancer cells may make their growth factors, have growth factor pathways
that are stuck in the "on" position, or, in the context of the body, even trick
neighboring cells into producing growth factors to sustain them.
 • Another hallmark of cancer cells is their "replicative immortality," a fancy term for the fact
that they can divide many more times than a normal cell of the body. In general, human cells
can go through only about 40-60 rounds of division before they lose the capacity to divide,
"grow old," and eventually die.
 Cancer cells also fail to undergo programmed cell death, or apoptosis, under conditions when
normal cells would (e.g., due to DNA damage). In addition, emerging research shows that
cancer cells may undergo metabolic changes that support increased cell growth and division
THANK YOU!
-GROUP 3