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Đinh Đoàn LongLÝ THUYẾT CƠ SỞ Trang 2 DDL@VNU-SMP Overview of today’s topics: 1.. The end replication problem and telomerase 2.. How cells repair replication mistakes 3.. Other types o
LY THUYET (CO SO) DI TRUYEN HOC NHIEM SAC THE PGS.TS Dinh Doan Long Overview of today’s topics: 1st theme DNA replication and repair The end replication problem and telomerase How cells repair replication mistakes Other types of DNA repair 2"¢ theme Meiosis and Genetic Variability Vocabulary of meiosis The process of meiosis Mistake in melosis and sex determination 3'4 theme Sex linkage and pedigrees How to know you are dealing with one or two genes X-linked inheritance Human pedigrees — ——— a J - DDL@VNU-SMP How is new DNA synthesized? Matt Meselson & Frank Stahl, 1958 They wanted to distinguish between different models for how DNA might be copied each gives rise to a new PHOT Phước, EPDM Hybrid ¿ š Generation 15N Generation Hybrid !4N Hybrid đại ý 14N After generations: 1/2 low-density DNA 1/2 intermediate-density DNA | he double-stranded structure i= Generation PDX complementary strand gives rise to a new Dispersive Double-stranded DNA replicated over short stretches ar Pm The strands separate and Conservative Double-stranded DNA Semi-conservative — a After generations: 1/4 high-density DNA 3/4 low-density DNA After generations: All intermediate-density DNA DDL@VNU-SMP Meselson-Stahl: Top of centrifuge tube (lower density) The results "S7 ~ ˆ 14N _ Hybrid — 15N Bottom of centrifuge tube (higher density) === —— ^” —— wu —- — _— *š After generations: 1/2 low-density DNA 1/2 intermediate-density DNA Ị NI „ Generation After generation 1: DNA all of intermediate density After generation 2: Y2 DNA of low density Y2 DNA of intermediate density This result was only consistent with semi-conservative replication, in which each parental strand is used to synthesize a complementary strand II DDL@VNU-SMP Let's take a closer look at what happens during DNA synthesis Deoxynucleoside triphosphates are added to a template DNA polymerase BẾP catalyzes this : is the enzyme that reaction annealed primer (A, G, C, or T) | Y o: : / growing end of DNA = _/template strand DDL@VNU-SMP DNA Is always synthesized in the 5’ > 3’ direction C- = a O Sas Oo ( oO ® ứ) = O > O O How can DNA be synthesized in both directions at the same time? B = ° z > — © a a The Replication Fork: DNA synthesis starts at an origin and proceeds in both directions (a) A chromosome being replicated (b) Bacterial chromosomes have a single point of origin _ § go pOPY, "eg > Đ :2 —~ § Bạn § “2À ay se \ IVP Mp %a dy > Old DNA —New DNA \ \ Replication/ / proceeds in Origin of both directions replication Replication (c) Eukaryotic chromosomes have multiple points of origin 09000%0%016z oo i | L7 0%0%.0%63 oe ` | 5, mms » 30%:0%40%63 Old DNA `New DNA ` Replication proceeds directions from each fork —_ =o —=Ää B ald Roles ®mŠ -›}` KVOVIVO in both starting noint > But what about the other strand? II DDL@VNU-SMP Solution: DNA synthesis is continuous on one strand (the leading strand) but discontinuous on the lagging strand T Nx / Newly iy Template strands r Unwinding— and replication synthesized DNA Lagging strand Okazaki fragments 53 Discontinuous SK 5:3 s On yes Leading strand Continuous DNA synthesis Bi-directional DNA synthesis starting at an origin of replication Okazaki fragments | Origin i Directionof fork movement = \ ` ¬ " Direction of fork movement — ⁄” Lagging HE Leading Laggino PA _— Origin Question: ae \ : Okazak| fragments Does point ‘A’ represent a 5’ or 3’ end of DNA? II DDL@VNU-SMP Leading strand synthesis: Primase synthesizes RNA primer Topoisomerase relieves twisting forces PY 5’ PUP VIVIVIVIVIVHU Helicase opens double helix Single-strand DNA-binding proteins (SSBP) stabilize single strands DNA is opened, unwound, and primed Sliding clamp holds DNA polymerase in place fi ‘j đd Si eo RNA primer Leading strand , “a DNA polymerase Ill works in 5— 3’ direction, synthesizing leading strand TRE La vs Àve.es KAA Th a at l/®› >/0)9?ao002020 00eh 00 0000%0044d048 ,P —| Synthesis of leading strand begins DDL@VNU-SMP