UMass Amherst BIOLOGY 285 - Bio SI Before Exam 3 (6 pages)

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Bio SI Before Exam 3



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Bio SI Before Exam 3

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Pages:
6
School:
University of Massachusetts Amherst
Course:
Biology 285 - Cellular & Molecular Biology
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Bio SI Before Exam 3 Herceptin Another example of a targeted cancer therapy Used to treat HER2 which is involved in breast cancer body overexpressing HER2 in breast cancer cells o Negative effect is not targeted to specific receptor will bind to whatever receptor it can bind to o Get a mutation in promoter gene that gets receptor to be overly expressed Monoclonal antibody not a small molecule antibodies are huge o Gleevec is a small molecule inhibitor Targets all HER2 receptors Antibodies Proteins that got produced by white blood cells Function is to bind to antigens which are foreign bodies non self ex viruses o Antibodies mark them for later destruction Variable domain where we get different variants of the antibodies Constant domain always the same Made up of heavy chain light chain one variable of each one constant of each 4 subunits Disulfide bond makes antibodies very stable Antigen bonds to variable because antigens can be anything can be different types so need antibody to be susceptible to bind to these How does variable region become variant o VDJ recombination Antibodies VDJ Recombination Variable region made up of V segments D segments and J segments o Regions in the DNA Recombination of the DNA makes up the variable region Can make up to 4 000 arrangements How can cell make sure it adds more variability to variant region o TDT polymerase that adds random nucleotides in between the segments o More than 4 000 antigens so need to add different nucleotides between segments to increase number of variability so can bind to all those antigens How does this cutting happen o RAG1 RAG2 cut DNA to make different segments and put them together o Same way CML cut Overview of Cell Cycle G1 phase growth gap phase o Could duplicate organelles o Cell checks environment Growth factor signals present Enough nutrients Enough energy DNA check for damage o Restriction point START G1 checkpoint prepare ingredients Make nucleotides Make proteins required for replication o Once replication starts cells now in S phase S phase synthesis phase o DNA replication G2 phase 2nd growth phase o Check for DNA damage o Finish replication o Prepare for M phase M phase chromosome segregation o Cytokinesis splitting of the cytosol G0 phase non dividing state Cell Cycle Control System CDK enzyme called Cyclin Dependent Kinase o Cyclin is binding partner o Master cell cycle regulator o Any point in cell cycle that cells decide they need to stop inhibit CDK CDK is regulated in several ways o Cyclin regulation different cyclins for different phases of the cell cycle G1 cyclins telling CDK to target G1 proteins S phase cyclins M phase cyclins o Phosphorylation dephosphorylation by kinases and phosphatases o CDK inhibitors Another way of regulation is the regulation of cyclin levels o Play with levels of cyclins themselves Cyclin levels rise fall throughout cell cycle via o Transcription translation o Degradation through ubiquitin mediated proteolysis o Eventually cause regulation of CDK not regulating CDK levels regulating the cyclin levels here things that bind to CDK Open response question on exam probably Cell Cycle Checkpoints G1 o Check for DNA damage before replication begins o Check for favorable environment o Must have enough material to create a duplication of the cell S o Check for errors incompletely duplicated DNA G2 o Damaged or incorrectly replicated DNA o Enough resources to continue M o Proper chromosome and microtubule attachment and arrangement G0 is rest phase when DNA damage too much to be fixed didn t get fixed etc P53 DNA Damage Response P53 is a tumor suppressor transcription factor that when activated promotes the transcription of the P21 gene other genes P21 gene is a CDK inhibitor o G1 S CDK S CDK inhibitor specifically inactivated by P21 Restriction Point Rb E2F Restriction point Start decision point point of no return o Happens in G1 o Protein levels rise Cyclin D o E2F is family of transcription factors o o o E2F up regulates proteins needed for S phase E2F is kept inhibited by Rb until there is enough cyclin levels in the cell the cell makes the decision to continue with the cell cycle Once Cyclin D CDK complex reaches a certain concentration Rb releases E2F and the cell can enter the cell cycle and express proteins for S phase Control of the Replicative Cycle Origin of replication complex Pre RC binds to origin replication o Pre RC made of ORC CDC6 CDT1 ORC origin of replication recruits a protein called Cdc6 which recruits Mcm complex helicase CDT1 recruits Mcm which is a helicase to the Pre RC complex o Mcm only protein involved in DNA replication This occurs from G1 S phase Once you start replicating in S phase How make sure replication doesn t happen back to back or twice at a time o S CDK regulation S CDK regulates ORC complex CDC6 Mcm Phosphorylation of ORC prevents association of ORC with CDT1 Mcm Phosphorylation of Cdc6 leads to degradation Phosphorylation of Mcm leads to export from the nucleus G2 Phase Prepping for Chromosome Segregation During G2 cyclin levels rising M CDK complexes forming but not active M phase cyclin CDK activity not occurring yet because of positive feedback loop M CDK pathway Mitotic CDK binds to M cyclin makes an inactive M CDK Wee1 inhibitory kinase Cak activating kinase adds a phosphate each to M CDK complex CDC25 activating phosphatase takes off inhibiting phosphate from Wee1 from M CDK active M CDK complex o CDC25 not active all the time o To activate more CDC25 need the positive feedback loop Longer you have M CDK inactive the longer you have to grow the cell therefore bigger the cell will be o Faster you are in activating M CDK less time to have right size causing you to get a smaller cell o Inactive Wee1 smaller cell less time to activate M CDK o Inactive CDC25 bigger cell longer time to activate M CDK Positive Feedback Loop Inactive CDC25 phosphatase gets phosphate from M CDK complex makes it an active CDC25 then goes and finds another inactive M CDK complex and takes the phosphate etc forever and ever Q How does CDK trigger onset of M phase o CDK phosphorylates laminin which leads to breakdown of nuclear envelope o Would lead into M phase segregation chromosome segregation o CDK phosphorylates condensin get sausage like chromosomes rather than spaghetti like chromosomes o CDK phosphorylates various MAPs microtubule associated proteins motor proteins which lead into the assembly of the spindle o CDK triggers M phase by phosphorylating


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