Chapter 3 Cells: The Living Units: Part D Cell Cycle

1. Chapter 3Cells: The Living Units: Part DCell Cycle • Defines changes from formation of the cell until it reproduces • Includes: • Interphase • Cell division (mitotic phase)

2. Interphase • Period from cell formation to cell division • Nuclear material called chromatin • Four subphases: • G1 (gap 1)—vigorous growth and metabolism • G0—gap phase in cells that permanently cease dividing • S (synthetic)—DNA replication • G2 (gap 2)—preparation for division

3. G1 checkpoint (restriction point) S Growth and DNA synthesis G2 Growth and final preparations for division G1 Growth M G2 checkpoint Figure 3.31

4. Centrosomes (each has 2 centrioles) Interphase Plasma membrane Nucleolus Chromatin Nuclear envelope Interphase Figure 3.33

5. DNA Replication • DNA helices begin unwinding from the nucleosomes • Helicase untwists the double helix and exposes complementary chains • The Y-shaped site of replication is the replication fork • Each nucleotide strand serves as a template for building a new complementary strand

6. DNA Replication • DNA polymerase only works in one direction • Continuous leading strand is synthesized • Discontinuous lagging strand is synthesized in segments • DNA ligase splices together short segments of discontinuous strand

7. DNA Replication • End result: two DNA molecules formed from the original • This process is called semiconservative replication

8. Old strand acts as a template for synthesis of new strand DNA polymerase Free nucleotides Chromosome Leading strand Two new strands (leading and lagging) synthesized in opposite directions Lagging strand Old DNA Helicase unwinds the double helix and exposes the bases Replication fork Adenine Thymine Cytosine DNA polymerase Old (template) strand Guanine Figure 3.32

9. DNA Replication PLAY Animation: DNA Replication

10. Cell Division • Mitotic (M) phase of the cell cycle • Essential for body growth and tissue repair • Does not occur in most mature cells of nervous tissue, skeletal muscle, and cardiac muscle

11. Cell Division • Includes two distinct events: • Mitosis—four stages of nuclear division: • Prophase • Metaphase • Anaphase • Telophase • Cytokinesis—division of cytoplasm by cleavage furrow

12. G1 checkpoint (restriction point) S Growth and DNA synthesis G2 Growth and final preparations for division G1 Growth M G2 checkpoint Figure 3.31

13. Cell Division PLAY A&P Flix™: Mitosis PLAY Animation: Mitosis

14. Prophase • Chromosomes become visible, each with two chromatids joined at a centromere • Centrosomes separate and migrate toward opposite poles • Mitotic spindles and asters form

15. Prophase • Nuclear envelope fragments • Kinetochore microtubules attach to kinetochore of centromeres and draw them toward the equator of the cell • Polar microtubules assist in forcing the poles apart

16. Early mitotic spindle Early Prophase Aster Chromosome consisting of two sister chromatids Centromere Early Prophase Figure 3.33

17. Polar microtubule Spindle pole Fragments of nuclear envelope Late Prophase Kinetochore Kinetochore microtubule Late Prophase Figure 3.33

18. Metaphase • Centromeres of chromosomes are aligned at the equator • This plane midway between the poles is called the metaphase plate

19. Metaphase Spindle Metaphase plate Metaphase Figure 3.33

20. Anaphase • Shortest phase • Centromeres of chromosomes split simultaneously—each chromatid now becomes a chromosome • Chromosomes (V shaped) are pulled toward poles by motor proteins of kinetochores • Polar microtubules continue forcing the poles apart

21. Anaphase Daughter chromosomes Anaphase Figure 3.33

22. Telophase • Begins when chromosome movement stops • The two sets of chromosomes uncoil to form chromatin • New nuclear membrane forms around each chromatin mass • Nucleoli reappear • Spindle disappears

23. Cytokinesis • Begins during late anaphase • Ring of actin microfilaments contracts to form a cleavage furrow • Two daughter cells are pinched apart, each containing a nucleus identical to the original

24. Nuclear envelope forming Nucleolus forming Contractile ring at cleavage furrow Telophase and Cytokinesis Telophase Figure 3.33

25. Control of Cell Division • “Go” signals: • Critical volume of cell when area of membrane is inadequate for exchange • Chemicals (e.g., growth factors, hormones, cyclins, and cyclin-dependent kinases (Cdks))

26. Control of Cell Division • “Stop” signals: • Contact inhibition • Growth-inhibiting factors produced by repressor genes

27. Protein Synthesis • DNA is the master blueprint for protein synthesis • Gene: Segment of DNA with blueprint for one polypeptide • Triplets of nucleotide bases form genetic library • Each triplet specifies coding for an amino acid PLAY Animation: DNA and RNA

28. Nuclear envelope DNA Transcription RNA Processing Pre-mRNA mRNA Nuclear pores Ribosome Translation Polypeptide Figure 3.34

29. Roles of the Three Main Types of RNA • Messenger RNA (mRNA) • Carries instructions for building a polypeptide, from gene in DNA to ribosomes in cytoplasm

30. Roles of the Three Main Types of RNA • Ribosomal RNA (rRNA) • A structural component of ribosomes that, along with tRNA, helps translate message from mRNA

31. Roles of the Three Main Types of RNA • Transfer RNAs (tRNAs) • Bind to amino acids and pair with bases of codons of mRNA at ribosome to begin process of protein synthesis

32. Transcription • Transfers DNA gene base sequence to a complementary base sequence of an mRNA • Transcription factor • Loosens histones from DNA in area to be transcribed • Binds to promoter, a DNA sequence specifying start site of gene to be transcribed • Mediates the binding of RNA polymerase to promoter

33. Transcription • RNA polymerase • Enzyme that oversees synthesis of mRNA • Unwinds DNA template • Adds complementary RNA nucleotides on DNA template and joins them together • Stops when it reaches termination signal • mRNA pulls off the DNA template, is further processed by enzymes, and enters cytosol

34. RNA polymerase Coding strand DNA Terminationsignal Promoterregion Template strand 1 Initiation: With the help of transcription factors, RNApolymerase binds to the promoter, pries apart the two DNA strands,and initiates mRNA synthesis at the start point on the template strand. Template strand mRNA Coding strand of DNA Rewindingof DNA Unwindingof DNA 2 Elongation: As the RNA polymerase moves along the templatestrand, elongating the mRNA transcript one base at a time, it unwindsthe DNA double helix before it and rewinds the double helix behind it. RNA nucleotides Direction oftranscription Templatestrand mRNA transcript DNA-RNA hybrid region mRNA RNApolymerase 3 Termination: mRNA synthesis ends when the termination signalis reached. RNA polymerase and the completed mRNA transcript arereleased. The DNA-RNA hybrid: At any given moment, 16–18 base pairs ofDNA are unwound and the most recently made RNA is still bound toDNA. This small region is called the DNA-RNA hybrid. Completed mRNA transcript RNA polymerase Figure 3.35

35. RNA polymerase Coding strand DNA Template strand Terminationsignal Promoterregion 1 Initiation: With the help of transcription factors, RNApolymerase binds to the promoter, pries apart the two DNA strands,and initiates mRNA synthesis at the start point on the template strand. Figure 3.35 step 1

36. Template strand mRNA 2 Elongation: As the RNA polymerase moves along the templatestrand, elongating the mRNA transcript one base at a time, it unwindsthe DNA double helix before it and rewinds the double helix behind it. mRNA transcript Figure 3.35 step 2

37. 3 Termination: mRNA synthesis ends when the termination signalis reached. RNA polymerase and the completed mRNA transcript arereleased. RNApolymerase Completed mRNA transcript Figure 3.35 step 3

38. Coding strand of DNA Rewindingof DNA Unwindingof DNA RNA nucleotides Direction oftranscription Templatestrand DNA-RNA hybrid region mRNA RNApolymerase The DNA-RNA hybrid: At any given moment, 16–18 base pairsof DNA are unwound and the most recently made RNA is stillbound to DNA. This small region is called the DNA-RNA hybrid. Figure 3.35 step 4

39. RNA polymerase Coding strand DNA Terminationsignal Promoterregion Template strand 1 Initiation: With the help of transcription factors, RNApolymerase binds to the promoter, pries apart the two DNA strands,and initiates mRNA synthesis at the start point on the template strand. Template strand mRNA Coding strand of DNA Rewindingof DNA Unwindingof DNA 2 Elongation: As the RNA polymerase moves along the templatestrand, elongating the mRNA transcript one base at a time, it unwindsthe DNA double helix before it and rewinds the double helix behind it. RNA nucleotides Direction oftranscription Templatestrand mRNA transcript DNA-RNA hybrid region mRNA RNApolymerase 3 Termination: mRNA synthesis ends when the termination signalis reached. RNA polymerase and the completed mRNA transcript arereleased. The DNA-RNA hybrid: At any given moment, 16–18 base pairs ofDNA are unwound and the most recently made RNA is still bound toDNA. This small region is called the DNA-RNA hybrid. Completed mRNA transcript RNA polymerase Figure 3.35

40. Translation • Converts base sequence of nucleic acids into the amino acid sequence of proteins • Involves mRNAs, tRNAs, and rRNAs

41. Genetic Code • Each three-base sequence on DNA is represented by a codon • Codon—complementary three-base sequence on mRNA

42. SECOND BASE U C A G U UUU UCU UAU UGU Tyr Cys Phe C UUC UCC UAC UGC U Ser A UUA UCA UAA Stop UGA Stop Leu G UUG UCG UAG Stop UGG Trp U CUU CCU CAU CGU His C CUC CCC CAC CGC C Leu Pro Arg A CUA CCA CAA CGA Gln G CUG CCG CAG CGG U AUU ACU AAU AGU Asn Ser C Ile AUC ACC AAC AGC A Thr A AUA ACA AAA AGA Lys Arg Met or G AUG ACG AAG AGG Start U GUU GCU GAU GGU Asp C GUC GCC GAC GGC G Val Ala Gly A GUA GCA GAA GGA Glu G GUG GCG GAG GGG Figure 3.36

43. Translation • mRNA attaches to a small ribosomal subunit that moves along the mRNA to the start codon • Large ribosomal unit attaches, forming a functional ribosome • Anticodon of a tRNA binds to its complementary codon and adds its amino acid to the forming protein chain • New amino acids are added by other tRNAs as ribosome moves along rRNA, until stop codon is reached

44. Nucleus Energized by ATP, the correct amino acid is attached to each species of tRNA by aminoacyl-tRNA synthetase enzyme. RNA polymerase mRNA Leu Template strand of DNA Amino acid 1 After mRNA synthesis in the nucleus, mRNA leaves the nucleus and attaches to a ribosome. Nuclear pore tRNA Nuclear membrane A G A 2 Translation begins as incoming aminoacyl-tRNA recognizes the complementary codon calling for it at the A site on the ribosome. It hydrogen-bonds to the codon via its anticodon. Released mRNA Aminoacyl-tRNA synthetase Leu 3 As the ribosome moves along the mRNA, and each codon is read in sequence, a new amino acid is added to the growing protein chain and the tRNA in the A site is translocated to the P site. Ile tRNA “head” bearing anticodon G A A Pro 4 Once its amino acid is released from the P site, tRNA is ratcheted to the E site and then released to reenter the cytoplasmic pool, ready to be recharged with a new amino acid. The polypeptide is released when the stop codon is read. U A U P site Large ribosomal subunit E site A site G C G A U U U A C C G C Small ribosomal subunit Codon 15 Codon 16 Codon 17 Direction of ribosome advance Portion of mRNA already translated Figure 3.37

45. Energized by ATP, the correct amino acid is attached to each species of tRNA by aminoacyl- tRNA synthetase enzyme. Nucleus RNA polymerase mRNA Template strand of DNA Leu Amino acid 1 After mRNA synthesis in the nucleus, mRNA leaves the nucleus and attaches to a ribosome. Nuclear pore tRNA Nuclear membrane A G A Released mRNA Aminoacyl-tRNA synthetase Figure 3.37 step 1

46. Leu 2 Translation begins as incoming aminoacyl-tRNA recognizes the complementary codon calling for it at the A site on the ribosome. It hydrogen-bonds to the codon via its anticodon. tRNA “head” bearing anticodon Ile G A A Pro U A U P site Large ribosomal subunit E site A site G C G A U U U A C C G C Small ribosomal subunit Codon 15 Codon 16 Codon 17 Direction of ribosome advance Portion of mRNA already translated Figure 3.37 step 2

47. Leu 3 As the ribosome moves along the mRNA, and each codon is read in sequence, a new amino acid is added to the growing protein chain and the tRNA in the A site is translocated to the P site. 2 Translation begins as incoming aminoacyl-tRNA recognizes the complementary codon calling for it at the A site on the ribosome. It hydrogen-bonds to the codon via its anticodon. tRNA “head” bearing anticodon Ile G A A Pro U A U P site Large ribosomal subunit E site A site G C G A U U U A C C G C Small ribosomal subunit Codon 15 Codon 16 Codon 17 Direction of ribosome advance Portion of mRNA already translated Figure 3.37 step 3

48. Leu 3 As the ribosome moves along the mRNA, and each codon is read in sequence, a new amino acid is added to the growing protein chain and the tRNA in the A site is translocated to the P site. 2 Translation begins as incoming aminoacyl-tRNA recognizes the complementary codon calling for it at the A site on the ribosome. It hydrogen-bonds to the codon via its anticodon. tRNA “head” bearing anticodon Ile G A A Pro 4 Once its amino acid is released from the P site, tRNA is ratcheted to the E site and then released to reenter the cytoplasmic pool, ready to be recharged with a new amino acid. The polypeptide is released when the stop codon is read. U A U P site Large ribosomal subunit E site A site G C G A U U U A C C G C Small ribosomal subunit Codon 15 Codon 16 Codon 17 Direction of ribosome advance Portion of mRNA already translated Figure 3.37 step 4

49. Nucleus Energized by ATP, the correct amino acid is attached to each species of tRNA by aminoacyl-tRNA synthetase enzyme. RNA polymerase mRNA Leu Template strand of DNA Amino acid 1 After mRNA synthesis in the nucleus, mRNA leaves the nucleus and attaches to a ribosome. Nuclear pore tRNA Nuclear membrane A G A 2 Translation begins as incoming aminoacyl-tRNA recognizes the complementary codon calling for it at the A site on the ribosome. It hydrogen-bonds to the codon via its anticodon. Released mRNA Aminoacyl-tRNA synthetase Leu 3 As the ribosome moves along the mRNA, and each codon is read in sequence, a new amino acid is added to the growing protein chain and the tRNA in the A site is translocated to the P site. Ile tRNA “head” bearing anticodon G A A Pro 4 Once its amino acid is released from the P site, tRNA is ratcheted to the E site and then released to reenter the cytoplasmic pool, ready to be recharged with a new amino acid. The polypeptide is released when the stop codon is read. U A U P site Large ribosomal subunit E site A site G C G A U U U A C C G C Small ribosomal subunit Codon 15 Codon 16 Codon 17 Direction of ribosome advance Portion of mRNA already translated Figure 3.37

50. Role of Rough ER in Protein Synthesis • mRNA–ribosome complex is directed to rough ER by a signal-recognition particle (SRP) • Forming protein enters the ER • Sugar groups may be added to the protein, and its shape may be altered • Protein is enclosed in a vesicle for transport to Golgi apparatus