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These are the user uploaded subtitles that are being translated: 0 00:00:00,000 --> 00:00:00,650 1 00:00:00,650 --> 00:00:03,830 Our bodies consist of trillions of cells. 2 00:00:03,830 --> 00:00:06,740 These cells need to divide when our bodies grow, 3 00:00:06,740 --> 00:00:09,150 replenish the cells we've lost from injuries, 4 00:00:09,150 --> 00:00:11,590 or need to maintain cell populations, like that 5 00:00:11,590 --> 00:00:13,150 of the skin. 6 00:00:13,150 --> 00:00:15,430 The mitotic cell cycle is the process 7 00:00:15,430 --> 00:00:19,010 by which all eukaryotic cells replicate and divide 8 00:00:19,010 --> 00:00:21,660 to produce daughter cells for growth, repair, 9 00:00:21,660 --> 00:00:23,150 and development. 10 00:00:23,150 --> 00:00:26,280 Because the cell cycle is vital to our survival, 11 00:00:26,280 --> 00:00:28,510 our cells tightly regulate the process 12 00:00:28,510 --> 00:00:31,690 to prevent uncontrolled cell division or incorrect DNA 13 00:00:31,690 --> 00:00:35,720 replication, which can lead to diseases, like cancer. 14 00:00:35,720 --> 00:00:37,800 This video gives an overview of the steps 15 00:00:37,800 --> 00:00:39,680 within the cell cycle, and introduces 16 00:00:39,680 --> 00:00:42,460 some of the key proteins that help our bodies regulate 17 00:00:42,460 --> 00:00:43,650 cell division. 18 00:00:43,650 --> 00:00:46,910 We will use language that is defined in our cell cycle terms 19 00:00:46,910 --> 00:00:47,710 video. 20 00:00:47,710 --> 00:00:49,580 So we recommend that you watch that video, 21 00:00:49,580 --> 00:00:52,520 if you haven't already done so. 22 00:00:52,520 --> 00:00:54,490 How, exactly, does the cell cycle 23 00:00:54,490 --> 00:00:59,330 enable DNA replication and cell division to produce more cells? 24 00:00:59,330 --> 00:01:02,590 We divide the cell cycle into four main phases-- 25 00:01:02,590 --> 00:01:07,900 G1, S, G2, and M. We group these phases 26 00:01:07,900 --> 00:01:09,990 into two more general phases-- 27 00:01:09,990 --> 00:01:11,770 interphase, during which the cell 28 00:01:11,770 --> 00:01:14,790 prepares for cell division, and the mitotic phase, 29 00:01:14,790 --> 00:01:17,260 when cell division occurs. 30 00:01:17,260 --> 00:01:20,130 In experimental assays, populations of cells 31 00:01:20,130 --> 00:01:22,945 can be either synchronous or asynchronous. 32 00:01:22,945 --> 00:01:25,230 A synchronous population of cells 33 00:01:25,230 --> 00:01:28,450 contains cells that are all in the same phase of the cell 34 00:01:28,450 --> 00:01:29,280 cycle-- 35 00:01:29,280 --> 00:01:32,160 for example, a cell culture with many cells 36 00:01:32,160 --> 00:01:35,550 that are all beginning mitosis simultaneously. 37 00:01:35,550 --> 00:01:37,900 Cells in an asynchronous population 38 00:01:37,900 --> 00:01:40,440 are spread throughout the cell cycle stages. 39 00:01:40,440 --> 00:01:43,220 For example, some cells will be in S phase, 40 00:01:43,220 --> 00:01:47,060 while others are in M phase and actively dividing. 41 00:01:47,060 --> 00:01:50,260 This video focuses on one phase of the human cell cycle 42 00:01:50,260 --> 00:01:52,670 at a time, paying specific attention 43 00:01:52,670 --> 00:01:57,120 to how much genetic material is in the cell at each point. 44 00:01:57,120 --> 00:01:59,220 Note that when cells are not dividing, 45 00:01:59,220 --> 00:02:03,450 they often enter a quiescent stage, called the G0 phase. 46 00:02:03,450 --> 00:02:06,120 These cells are performing their unique functions, 47 00:02:06,120 --> 00:02:09,490 but are not undergoing cell growth or division. 48 00:02:09,490 --> 00:02:11,600 Because these cells are not dividing, 49 00:02:11,600 --> 00:02:16,320 they will have 46 homologous chromosomes, or 2N chromosomes, 50 00:02:16,320 --> 00:02:20,520 no sister chromatids, and 2C DNA content, 51 00:02:20,520 --> 00:02:22,920 because the cell is diploid and no DNA 52 00:02:22,920 --> 00:02:25,450 replication has occurred. 53 00:02:25,450 --> 00:02:30,020 The G1, or Gap 1, phase involves cell growth and preparation 54 00:02:30,020 --> 00:02:34,090 for DNA replication, which will take place in S phase. 55 00:02:34,090 --> 00:02:35,780 This preparation includes checking 56 00:02:35,780 --> 00:02:38,180 for cells with DNA damage, making 57 00:02:38,180 --> 00:02:41,680 sure there are enough nutrients in the cell for cell division, 58 00:02:41,680 --> 00:02:45,440 and verifying that the cell is big enough to divide. 59 00:02:45,440 --> 00:02:47,830 During the G1 phase, the cell also 60 00:02:47,830 --> 00:02:51,380 prepares for initiation of DNA replication. 61 00:02:51,380 --> 00:02:55,800 Specifically, proteins identify origins of replication and load 62 00:02:55,800 --> 00:02:58,860 multi-protein complexes onto this DNA, 63 00:02:58,860 --> 00:03:02,110 for example, the DNA helicase. 64 00:03:02,110 --> 00:03:03,860 How many chromosomes are currently 65 00:03:03,860 --> 00:03:06,160 in the cell after G1 phase? 66 00:03:06,160 --> 00:03:07,370 Try to fill out this table. 67 00:03:07,370 --> 00:03:12,490 68 00:03:12,490 --> 00:03:14,880 Right now, the diploid eukaryotic cell 69 00:03:14,880 --> 00:03:18,870 has 2N chromosomes, 46 in humans. 70 00:03:18,870 --> 00:03:22,790 The cell modified the DNA to prepare for DNA replication. 71 00:03:22,790 --> 00:03:26,070 But no replication has occurred and, therefore, 72 00:03:26,070 --> 00:03:28,410 the number of chromosomes and genetic material 73 00:03:28,410 --> 00:03:30,840 is still the same as in G0. 74 00:03:30,840 --> 00:03:33,500 That is, sister chromatids have not formed 75 00:03:33,500 --> 00:03:37,570 and the cell has 2C DNA content because the cell is diploid 76 00:03:37,570 --> 00:03:40,690 and no DNA replication has occurred. 77 00:03:40,690 --> 00:03:43,700 At the end of G1, there's a point of no return, 78 00:03:43,700 --> 00:03:45,510 often called the restriction point, 79 00:03:45,510 --> 00:03:47,970 where the cell commits to completing the rest of the cell 80 00:03:47,970 --> 00:03:51,800 cycle and transitions into the S phase. 81 00:03:51,800 --> 00:03:55,960 DNA replication occurs in the S, or synthesis, phase. 82 00:03:55,960 --> 00:04:00,070 The cell now activates the DNA helicases that the cell loaded 83 00:04:00,070 --> 00:04:02,810 onto DNA in G1 phase. 84 00:04:02,810 --> 00:04:05,590 This process separates the double-stranded DNA 85 00:04:05,590 --> 00:04:08,380 into single-stranded DNA to provide the templates 86 00:04:08,380 --> 00:04:10,100 for DNA replication. 87 00:04:10,100 --> 00:04:12,580 The sites of helicase action are junctions 88 00:04:12,580 --> 00:04:15,490 between double-stranded and single-stranded DNA, 89 00:04:15,490 --> 00:04:17,640 which form replication forks. 90 00:04:17,640 --> 00:04:20,690 Many other proteins assemble at these sites, like DNA 91 00:04:20,690 --> 00:04:25,670 polymerase, primase, and others, to replicate the DNA strands. 92 00:04:25,670 --> 00:04:28,830 The cell does not load helicases during S phase, 93 00:04:28,830 --> 00:04:33,070 to ensure that the DNA is replicated once and only once. 94 00:04:33,070 --> 00:04:36,360 DNA replication results in duplicated chromosomes, 95 00:04:36,360 --> 00:04:38,460 sister chromatids that are held together 96 00:04:38,460 --> 00:04:41,840 by proteins that promote sister chromatid cohesion. 97 00:04:41,840 --> 00:04:44,760 Remember that sister chromatids are identical copies 98 00:04:44,760 --> 00:04:46,640 of a single chromosome. 99 00:04:46,640 --> 00:04:49,390 Now how many chromosomes are currently in the cell, 100 00:04:49,390 --> 00:04:50,530 after S phase? 101 00:04:50,530 --> 00:04:52,400 And how many copies of the DNA? 102 00:04:52,400 --> 00:04:53,765 Try to fill out this table. 103 00:04:53,765 --> 00:04:58,640 104 00:04:58,640 --> 00:05:02,060 Right now, the cell is still 2N, with 46 105 00:05:02,060 --> 00:05:04,330 unique homologous chromosomes. 106 00:05:04,330 --> 00:05:06,580 The DNA replication duplicates each 107 00:05:06,580 --> 00:05:10,010 of these individual chromosomes to form 46 pairs 108 00:05:10,010 --> 00:05:12,300 of identical sister chromatids. 109 00:05:12,300 --> 00:05:17,000 And there's 4C DNA content now, because DNA replication has 110 00:05:17,000 --> 00:05:20,130 occurred in this diploid cell. 111 00:05:20,130 --> 00:05:22,970 G2 phase is a gap phase that allows the cell 112 00:05:22,970 --> 00:05:26,150 to prepare for N phase, during which the cell will divide 113 00:05:26,150 --> 00:05:27,160 in two. 114 00:05:27,160 --> 00:05:29,640 This preparation mainly includes verifying 115 00:05:29,640 --> 00:05:32,790 that S phase completed correctly and that the chromosomes were 116 00:05:32,790 --> 00:05:35,280 completely and accurately replicated, 117 00:05:35,280 --> 00:05:39,660 with no need for DNA repair or further DNA replication. 118 00:05:39,660 --> 00:05:43,640 Now how many chromosomes are currently in the cell after G2, 119 00:05:43,640 --> 00:05:45,860 and how many copies of the DNA? 120 00:05:45,860 --> 00:05:47,055 Try to fill out this table. 121 00:05:47,055 --> 00:05:50,090 122 00:05:50,090 --> 00:05:53,350 Right now, the cell is still in the exact same state 123 00:05:53,350 --> 00:05:55,620 as it was at the end of S phase. 124 00:05:55,620 --> 00:05:59,540 There are 2N, or 46 unique homologous chromosomes, 125 00:05:59,540 --> 00:06:01,380 that have been duplicated to form 126 00:06:01,380 --> 00:06:04,090 46 pairs of sister chromatids. 127 00:06:04,090 --> 00:06:07,220 Because DNA replication occurred in S phase, 128 00:06:07,220 --> 00:06:11,260 there's still 4C DNA contents in the cell. 129 00:06:11,260 --> 00:06:15,200 Chromosome segregation occurs during M phase, or mitosis. 130 00:06:15,200 --> 00:06:17,830 We divide mitosis into subphases-- 131 00:06:17,830 --> 00:06:22,280 prophase, metaphase, anaphase, and telophase, directly 132 00:06:22,280 --> 00:06:25,540 followed by cytokinesis, or cell division. 133 00:06:25,540 --> 00:06:28,120 Prophase is when the pairs of sister chromatids 134 00:06:28,120 --> 00:06:30,990 condense to form the familiar chromosome shapes we 135 00:06:30,990 --> 00:06:33,070 see in textbook illustrations. 136 00:06:33,070 --> 00:06:35,810 The nuclear envelope in the cell also breaks down. 137 00:06:35,810 --> 00:06:38,370 To simplify these animations, we only 138 00:06:38,370 --> 00:06:42,600 show 3 of the 46 pairs of sister chromatids in a human cell. 139 00:06:42,600 --> 00:06:45,000 But keep in mind that the remaining pairs are still 140 00:06:45,000 --> 00:06:45,850 there. 141 00:06:45,850 --> 00:06:48,970 Metaphase is when the mitotic spindle forms. 142 00:06:48,970 --> 00:06:51,120 This structure is a molecular machine 143 00:06:51,120 --> 00:06:53,130 that separates the sister chromatids, 144 00:06:53,130 --> 00:06:55,130 ensuring that each daughter cell gets 145 00:06:55,130 --> 00:06:57,290 one copy of each chromosome. 146 00:06:57,290 --> 00:06:59,520 During metaphase, the filaments-- 147 00:06:59,520 --> 00:07:03,090 microtubules from the poles of the mitotic spindle, 148 00:07:03,090 --> 00:07:04,330 centrosomes-- 149 00:07:04,330 --> 00:07:06,770 attach to the pairs of sister chromatids 150 00:07:06,770 --> 00:07:10,320 on both sides of the region called the centromere. 151 00:07:10,320 --> 00:07:12,240 The tension from mitotic filaments, 152 00:07:12,240 --> 00:07:14,170 pulling the pairs of sister chromatids 153 00:07:14,170 --> 00:07:16,710 toward the opposite poles of the mitotic spindle, 154 00:07:16,710 --> 00:07:19,830 aligns the chromosomes in the center of the cell. 155 00:07:19,830 --> 00:07:22,930 This is called the metaphase plate. 156 00:07:22,930 --> 00:07:26,160 Anaphase is when the sister chromatids separate and are 157 00:07:26,160 --> 00:07:29,770 pulled to opposite sides of the cell by the mitotic spindle. 158 00:07:29,770 --> 00:07:31,900 Now each side of the cell, which will 159 00:07:31,900 --> 00:07:34,050 become one of the two daughter cells, 160 00:07:34,050 --> 00:07:37,680 has a complete set of 46 chromosomes. 161 00:07:37,680 --> 00:07:39,920 During telophase, the nuclear envelope 162 00:07:39,920 --> 00:07:42,160 begins to re-form around each group 163 00:07:42,160 --> 00:07:44,650 of segregated chromosomes. 164 00:07:44,650 --> 00:07:48,830 These chromosomes also begin to decondense once more. 165 00:07:48,830 --> 00:07:52,120 Cytokinesis is not technically a phase of mitosis, 166 00:07:52,120 --> 00:07:54,260 but follows immediately afterward. 167 00:07:54,260 --> 00:07:57,740 During cytokinesis, the plasma membrane of the mother cell 168 00:07:57,740 --> 00:08:00,150 fuses in a way that physically separates 169 00:08:00,150 --> 00:08:02,670 the cytoplasm of the mother cell to form 170 00:08:02,670 --> 00:08:05,530 two daughter cells, each with their own nucleus 171 00:08:05,530 --> 00:08:07,530 and chromosomes. 172 00:08:07,530 --> 00:08:10,060 Now how many chromosomes are currently 173 00:08:10,060 --> 00:08:11,510 in each daughter cell? 174 00:08:11,510 --> 00:08:13,790 And how many copies of the DNA? 175 00:08:13,790 --> 00:08:14,960 Try to fill out this table. 176 00:08:14,960 --> 00:08:19,710 177 00:08:19,710 --> 00:08:22,460 Each daughter cell is 2N, with 46 178 00:08:22,460 --> 00:08:24,830 unique homologous chromosomes. 179 00:08:24,830 --> 00:08:27,850 The pairs of sister chromatids have separated and are now 180 00:08:27,850 --> 00:08:31,010 just considered to be individual chromosomes in each 181 00:08:31,010 --> 00:08:32,440 of the daughter cells. 182 00:08:32,440 --> 00:08:36,010 Each new cell now only has two 2C DNA content, 183 00:08:36,010 --> 00:08:38,010 like all diploid cells. 184 00:08:38,010 --> 00:08:40,960 Now the cell cycle is ready to start all over again, 185 00:08:40,960 --> 00:08:42,799 with each of these daughter cells, 186 00:08:42,799 --> 00:08:47,130 or the cells can stop growing and arrest in the G0 phase. 187 00:08:47,130 --> 00:08:50,030 The cell cycle involves many steps, all of which 188 00:08:50,030 --> 00:08:52,960 are equally important to ensure that the replication 189 00:08:52,960 --> 00:08:56,940 of genetic material and cell division goes correctly. 190 00:08:56,940 --> 00:08:59,990 Now that you're familiar with the phases of the cell cycle, 191 00:08:59,990 --> 00:09:03,020 let's talk about what regulates these phases. 192 00:09:03,020 --> 00:09:05,430 How does the cell know what phase it's in, 193 00:09:05,430 --> 00:09:07,580 and how does it know that it's safe to proceed 194 00:09:07,580 --> 00:09:09,540 to the next phase? 195 00:09:09,540 --> 00:09:12,530 The cell cycle is regulated by a class of proteins called 196 00:09:12,530 --> 00:09:16,370 cyclins which, in turn, activate cyclin-dependent kinases, 197 00:09:16,370 --> 00:09:17,860 or CDKs. 198 00:09:17,860 --> 00:09:20,400 The name cyclin reflects their property 199 00:09:20,400 --> 00:09:23,300 of fluctuating in abundance in specific ways 200 00:09:23,300 --> 00:09:27,060 during the cell cycle, as you can see in this diagram. 201 00:09:27,060 --> 00:09:30,480 The abundance of cyclin and cyclin CDK activity 202 00:09:30,480 --> 00:09:33,180 divide the cell cycle into the distinct phases 203 00:09:33,180 --> 00:09:34,870 we described before-- 204 00:09:34,870 --> 00:09:38,060 G1, S, G2, and M. 205 00:09:38,060 --> 00:09:40,680 In addition, there are checkpoints during the cell 206 00:09:40,680 --> 00:09:43,320 cycle that check the work of the cell 207 00:09:43,320 --> 00:09:45,450 and ensure that one phase is complete 208 00:09:45,450 --> 00:09:47,390 before the next is started. 209 00:09:47,390 --> 00:09:49,480 For example, there's a checkpoint 210 00:09:49,480 --> 00:09:52,790 that prevents cells from entering mitosis until DNA 211 00:09:52,790 --> 00:09:54,820 replication is complete. 212 00:09:54,820 --> 00:09:57,020 This prevents catastrophic errors, 213 00:09:57,020 --> 00:10:00,410 such as segregating incompletely replicated chromosomes, which 214 00:10:00,410 --> 00:10:03,360 would lead to chromosome breaks and DNA damage, 215 00:10:03,360 --> 00:10:07,110 which could in turn lead to diseases like cancer. 216 00:10:07,110 --> 00:10:11,000 The cell cycle is essential for our growth and survival. 217 00:10:11,000 --> 00:10:13,290 The cell cycle can appear complicated 218 00:10:13,290 --> 00:10:16,340 because it integrates many smaller, equally complicated 219 00:10:16,340 --> 00:10:20,870 cellular processes, such as DNA replication and mitosis. 220 00:10:20,870 --> 00:10:22,600 Now that you've finished this video, 221 00:10:22,600 --> 00:10:24,760 can you explain the four different stages 222 00:10:24,760 --> 00:10:27,720 of the cell cycle, and what occurs in each step? 223 00:10:27,720 --> 00:10:30,960 And do you have an idea of what role cyclin and CDKs play 224 00:10:30,960 --> 00:10:33,280 in regulating the cell cycle, and why 225 00:10:33,280 --> 00:10:35,980 they are important to our overall health? 226 00:10:35,980 --> 00:10:37,920 Thanks for watching. 227 00:10:37,920 --> 00:10:42,858 17253

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