cell cycle regulation and cancer genes

why is cell division important to all organisms?

allows a cell to grow, accurately duplicate its genetic material, and divide into two genetically identical daughter cells

what is differentiation?

the biological process by which an unspecialized cell (i.e stem cell) changes into a more specialized cell type w/ a distinct structure + function (such as a nerve, muscle, or blood cell).

apoptosis

orderly or genetically regulated process of programmed cell death (cell suicide)

what is the difference between quiescence and senescence?

quiescence: reversible state where cells can re enter the cell cycle and start dividing once they get the nutrients they need

senescence: irreversible state, permanent cell-cycle arrest; cells cannot resume division under normal physiological conditions.

what are cell cycle regulators? what are some exs?

specialized proteins, enzymes, signaling molecules that coordinate, drive, pause, or stop the progression of a cell through its growth and division cycle

ex) cyclins, cyclin-dependent kinase, CDK inhibitors, Anaphase-Promoting Complex/Cyclosome

what is a cyclins role in cell cycle regulation?

control progression through the cell cycle by binding to and activating cyclin-dependent kinases (CDKs)

what is a cyclin-dependent kinase role in cell cycle regulation?

CDKs are present throughout the cell cycle, but they are inactive on their own. They require binding to regulatory proteins called cyclins to become active enzymes.

Enzymes (such as CDK1, CDK2, CDK4, and CDK6) that are present in constant amounts inside the cell but remain inactive until they bind to a specific cyclin. Once activated, they add phosphate groups to target proteins to propel the cell forward.

Cas9 protein

enzyme in CRISPR technology that act as molecular scissors that cut DNA

guide RNA (gRNA)

one sided strand of DNA bases, can be made in laboratories

use of viral vectors with CRISPR

viruses used to deliver CRISPR gene-editing enzymes (i.e Cas9 proteins + gRNAs) into target cells. they are small + non-enveloped, good at entering cells.

how do researchers use CRISPR?

 helps scientists test what genes do by changing them and observing the results. Researchers can:

• Knock out a gene and observe what changes.

• Turn a gene’s activity up or down.

• Change a gene’s function.

• Add a gene.

stages of CRSIPR

1. targeting: Scientists introduce the Cas9-guide RNA complex into a cell (in this case, a human cell), where it randomly associates and dissociates with the DNA. Cas9 recognizes and binds to a three-nucleotide sequence motif called PAM that is abundant throughout the genome.

2. binding: Once it binds to a PAM motif, Cas9 unwinds the DNA double helix. If the DNA at that location perfectly matches a sequence of about 20 nucleotides within the guide RNA, the DNA and matching RNA will bind through complementary base pairing.

3. cleaving: The DNA-RNA pairing triggers Cas9 to change its three-dimensional structure and activates its nuclease activity. Cas9 cleaves both DNA strands at a site upstream of PAM.

4. DNA repair: Cells contain enzymes that repair double-stranded DNA breaks. The repair process is naturally error-prone and will lead to mutations that may inactivate a gene. Cleaving DNA at a precise location is one of many applications of the CRISPR-Cas9 technology.

Two ways cells can repair the cut

1. Non-homologous end joining: The cell reconnects the broken DNA ends. This repair can add or remove small pieces of DNA, called insertions or deletions (indels). Indels may disrupt a gene and stop it from working—a result called a gene knockou

2. Homology-directed repair: If a DNA template is available, the cell may use it as a pattern to repair the break. Scientists can use a template to add or replace a DNA sequence.

*Scientists cannot always control which repair pathway the cell will use. The desired edit may not happen in every cell. DNA cuts can also cause unintended changes at or near the target.

2 classes of cancer causing genes

1 tumor suppressor genes; suppress cancerous growths. if both copies are mutated, it causes

2 Onco genes: a mutated or overactive gene that has the potential to cause normal cells to transform into cancer cells

onco vs. proto-onco genes

proto: These are normal, healthy genes that regulate critical cellular processes like growth, division, and programmed cell death (apoptosis). They function like a car's accelerator pedal

onco: When a proto-oncogene suffers a permanent mutation, gene duplication, or chromosomal rearrangement, it turns into an oncogene. This leaves the cellular accelerator stuck "on," forcing the cell to multiply uncontrollably and resist natural death

Kinase

Phosphotases