BIOLOGY 2B03 Lecture Notes - Lecture 19: Spindle Apparatus, Sister Chromatids, Nuclear Membrane
3 May 2018
School
Department
Course
Professor
Cell$cycle$
G1$
The$cell$ is$actively$growing,$engaged$in$gene$expression$and$the$synthesis$of$new$proteins
-
•
S-phase$
The$replication$ of$the$entire$genome$of$a$cell
-
•
G2$
A$second$gap$phase
-
•
Mitosis$
The$replicated$ sister$chromatids$are$precisely$ separated$to$the$two$daughter$cells
-
•
G0$
A$daughter$cell$may$cease$cell$division$and$enter$this$short$period$of$inactivity$before$re-entering$
the$cell$ cycle$
-
Or$this$cell$begins$the$step-wise$process$of$differentiation$to$become$a$specific$type$of$cell,$and$
will$no$longer$be$capable$of$cell$division$
-
This$balance$between$division$and$differentiation$is$important,$as$too$much$division$results$in$
tumors$and$too$much$differentiation$leads$to$an$inability$to$regenerate$ and$replace$ lost$tissue$$
-
•
Mitosis$
Prophase$
The$chromosomes$begin$the$process$of$condensation$
-
Assembly$of$the$mitotic$spindle$also$begins$as$the$duplicated$centrosomes$separate$to$opposite$
sides$of$the$cell$
-
Dissolution$of$the$nuclear$envelope$and$the$breakdown$of$the$endomembranes$of$the$cell$into$
small$vesicles$
-
•
Prometaphase$
The$chromosomes$are$maximally$condensed$and$are$in$the$process$of$attaching$their$
centromeres$to$the$fully$formed$bipolar$microtubule$spindle$
-
Kinetochore$proteins$assemble$at$the$centromeres$to$mediate$the$association$with$the$plus-ends$
of$the$spindle$microtubules$
-
•
Metaphase$
Chromosomes$are$attached$to$the$spindle$microtubules$from$both$poles$of$the$mitotic$spindle$
(this$is$known$as$bipolar$attachment)
-
The$forces$pulling$a$duplicated$chromosome$simultaneously$towards$both$poles$causes$the$
chromosomes$to$aggregate$in$the$middle$of$the$mitotic$spindle$
-
•
Anaphase$
The$sister$chromatids$are$pulled$towards$opposite$poles$of$the$spindle$and$they$are$separated
-
•
Telophase$
The$cell$ reverses$the$changes$that$occurred:$chromosomes$de-condense,$the$spindle$
disassembles,$the$nuclear$envelope$and$endomembrane$systems$reassemble$
-
•
The$Cell$ Cycle$
The$cell$ cycle$is$regulated$by$phosphorylated$cyclin-Cdk$complexes$and$degradation$via$E3$ligase$
complexes$
•
There$are$4$cyclin$cdk$kinases$and$3$E3$ligase$complexes$involved$with$the$cycle$•
Steps:$
Step$1$
G1$cyclin-CDK$inactivates$APC-Cdh1$by$phosphorylating$it,$resulting$in$the$signal$that$
mitosis$is$completed$
-
G1$cyclin-CDK$targets$transcription$factors$for$phosphorylating,$leading$to$the$concerted$
expression$of$S-phase$proteins$
-
G1$cyclin-CDK$phosphorylates$S-phase$inhibitor,$Sic1$
-
1.
Step$2$
SCF$degrades$the$phosphorylated$$Sic1
-
The$S-phase$cyclin-CDK$is$now$active$and$S-phase$can$begin$$
-
2.
Step$3$
G1/S-phase$cyclin-CDK$target$transcription$factors$that$regulate$the$expression$of$genes$
coding$for$mitosis$(including$M-phase$cyclins)
-
S$phase$cyclin-CDK$activates$the$assembly$of$the$pre-replication$complex$at$sites$of$origins$
of$replication$
-
These$proteins$associated$with$origins$of$replication$make$sure$that$the$origins$only$copy$
once$per$cell$cycle$
-
3.
Step$4$
M-phase$cyclin-CDK$phosphorylates$many$targets$which$result$in:$chromosome$
condensation,$the$breakdown$of$the$nuclear$envelope,$the$formation$of$mitotic$spindle$
proteins,$kinetochore$proteins$and$phosphorylated$APCs$$
-
4.
Step$5$
APC-Cdc20$degrades$securin$(made$of$a$collection$of$cohesion$proteins:$Smc1,$Smc2$and$
Smc3),$a$anaphase$inhibitor$protein$that$secures$the$two$replicated$sister$chromatids
-
This$activates$separase$which$cleaves$Smc1,$which$breaks$apart$the$cohesion$complex$$and$
allows$for$the$sister$chromatids$to$be$pulled$apart$
-
5.
Step$6$
Cyclin$B$is$degraded$by$APC-Cdh1after$telophase,$which$marks$the$end$of$mitosis$
-
6.
•
Scientific$test$results$
Cyclin$B$regulates$M-phase$cyclin$CDK$activity$•
Cyclin$B$must$be$degraded$to$allow$a$cell$ to$exit$mitosis•
Cyclin$B$activates$CDK$•
APC$has$a$target$sequences$called$the$D$box$•
Module'9:'Lecture'1
Tuesday,$ April$3,$2018
12:57$PM
Cell$cycle$
G1$
The$cell$ is$actively$growing,$engaged$in$gene$expression$and$the$synthesis$of$new$proteins
-
•
S-phase$
The$replication$ of$the$entire$genome$of$a$cell
-
•
G2$
A$second$gap$phase
-
•
Mitosis$
The$replicated$ sister$chromatids$are$precisely$ separated$to$the$two$daughter$cells
-
•
G0$
A$daughter$cell$may$cease$cell$division$and$enter$this$short$period$of$inactivity$before$re-entering$
the$cell$ cycle$
-
Or$this$cell$begins$the$step-wise$process$of$differentiation$to$become$a$specific$type$of$cell,$and$
will$no$longer$be$capable$of$cell$division$
-
This$balance$between$division$and$differentiation$is$important,$as$too$much$division$results$in$
tumors$and$too$much$differentiation$leads$to$an$inability$to$regenerate$ and$replace$ lost$tissue$$
-
•
Mitosis$
Prophase$
The$chromosomes$begin$the$process$of$condensation$
-
Assembly$of$the$mitotic$spindle$also$begins$as$the$duplicated$centrosomes$separate$to$opposite$
sides$of$the$cell$
-
Dissolution$of$the$nuclear$envelope$and$the$breakdown$of$the$endomembranes$of$the$cell$into$
small$vesicles$
-
•
Prometaphase$
The$chromosomes$are$maximally$condensed$and$are$in$the$process$of$attaching$their$
centromeres$to$the$fully$formed$bipolar$microtubule$spindle$
-
Kinetochore$proteins$assemble$at$the$centromeres$to$mediate$the$association$with$the$plus-ends$
of$the$spindle$microtubules$
-
•
Metaphase$
Chromosomes$are$attached$to$the$spindle$microtubules$from$both$poles$of$the$mitotic$spindle$
(this$is$known$as$bipolar$attachment)
-
The$forces$pulling$a$duplicated$chromosome$simultaneously$towards$both$poles$causes$the$
chromosomes$to$aggregate$in$the$middle$of$the$mitotic$spindle$
-
•
Anaphase$
The$sister$chromatids$are$pulled$towards$opposite$poles$of$the$spindle$and$they$are$separated
-
•
Telophase$
The$cell$ reverses$the$changes$that$occurred:$chromosomes$de-condense,$the$spindle$
disassembles,$the$nuclear$envelope$and$endomembrane$systems$reassemble$
-
•
The$Cell$ Cycle$
The$cell$ cycle$is$regulated$by$phosphorylated$cyclin-Cdk$complexes$and$degradation$via$E3$ligase$
complexes$
•
There$are$4$cyclin$cdk$kinases$and$3$E3$ligase$complexes$involved$with$the$cycle$•
Steps:$
Step$1$
G1$cyclin-CDK$inactivates$APC-Cdh1$by$phosphorylating$it,$resulting$in$the$signal$that$
mitosis$is$completed$
-
G1$cyclin-CDK$targets$transcription$factors$for$phosphorylating,$leading$to$the$concerted$
expression$of$S-phase$proteins$
-
G1$cyclin-CDK$phosphorylates$S-phase$inhibitor,$Sic1$
-
1.
Step$2$
SCF$degrades$the$phosphorylated$$Sic1
-
The$S-phase$cyclin-CDK$is$now$active$and$S-phase$can$begin$$
-
2.
Step$3$
G1/S-phase$cyclin-CDK$target$transcription$factors$that$regulate$the$expression$of$genes$
coding$for$mitosis$(including$M-phase$cyclins)
-
S$phase$cyclin-CDK$activates$the$assembly$of$the$pre-replication$complex$at$sites$of$origins$
of$replication$
-
These$proteins$associated$with$origins$of$replication$make$sure$that$the$origins$only$copy$
once$per$cell$cycle$
-
3.
Step$4$
M-phase$cyclin-CDK$phosphorylates$many$targets$which$result$in:$chromosome$
condensation,$the$breakdown$of$the$nuclear$envelope,$the$formation$of$mitotic$spindle$
proteins,$kinetochore$proteins$and$phosphorylated$APCs$$
-
4.
Step$5$
APC-Cdc20$degrades$securin$(made$of$a$collection$of$cohesion$proteins:$Smc1,$Smc2$and$
Smc3),$a$anaphase$inhibitor$protein$that$secures$the$two$replicated$sister$chromatids
-
This$activates$separase$which$cleaves$Smc1,$which$breaks$apart$the$cohesion$complex$$and$
allows$for$the$sister$chromatids$to$be$pulled$apart$
-
5.
Step$6$
Cyclin$B$is$degraded$by$APC-Cdh1after$telophase,$which$marks$the$end$of$mitosis$
-
6.
•
Scientific$test$results$
Cyclin$B$regulates$M-phase$cyclin$CDK$activity$•
Cyclin$B$must$be$degraded$to$allow$a$cell$ to$exit$mitosis•
Cyclin$B$activates$CDK$•
APC$has$a$target$sequences$called$the$D$box$•
Module'9:'Lecture'1
Tuesday,$ April$3,$2018 12:57$PM
Document Summary
The cell is actively growing, engaged in gene expression and the synthesis of new pro. The replication of the entire genome of a cell. The replicated sister chromatids are precisely separated to the two daughter cells. A daughter cell may cease cell division and enter this short period of inactivity befor the cell cycle. Or this cell begins the step-wise process of differentiation to become a specific type will no longer be capable of cell division. This balance between division and differentiation is important, as too much division tumors and too much differentiation leads to an inability to regenerate and replace. Assembly of the mitotic spindle also begins as the duplicated centrosomes separate sides of the cell. Dissolution of the nuclear envelope and the breakdown of the endomembranes of th small vesicles. The chromosomes are maximally condensed and are in the process of attaching thei centromeres to the fully formed bipolar microtubule spindle.
