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DNA Replication

Announcements:

• graded exams (and homework assignments, etc) will be returned this coming Monday in class

Learning objectives for Wed 11/15/00

Students should be able to…

1. describe the purpose of replication origins and the features they share in bacteria, yeast, and higher eukaryotic cells
2. state the three replication problems encountered by DNA polymerases and describe the solutions to these problems
3. compare and contrast the coordinated synthesis of leading and lagging strands in prokaryotes and eukaryotes. Identify and describe the roles of the proteins at the growing replication fork.

Outline:

• in most organisms, DNA replication is bidirectional and originates from repetitive, AT-rich sites (e.g., oriC, ARS) in the genome
• DNA polymerases do not possess intrinsic helicase functions, so they must rely on extrinsic helicases (e.g., DnaB) and accessory factors for opening of the DNA helix.
• DNA polymerases cannot inititate DNA synthesis; they only elongate preexisting DNA or RNA strands (e.g., primers).
• DNA polymerases only elongate DNA in a 5'->3' direction, but the strands in a DNA duplex have opposite polarity (i.e., 5'->3', 3'->5'). Thus, the leading strand is synthesized continuously by one replication complex that is tethered by a protein (e.g., tau in bacteria) to a separate replication complex on the lagging strand which is synthesized in a discontinuous fashion.

General outline for Chapter 12:

• Wed 11/15/00: Prokaryotic and eukaryotic DNA replication
• Fri 11/17/00: Telomeres, supercoiling and topoisomerases, types of DNA damage, proof-reading during replication, introduction to DNA mismatch repair
• Mon 11/20/00: Mismatch repair, base and nucleotide excision repair, error-prone repair, introduction to recombination
• Wed 11/21/00: Mechanisms of DNA recombination, role of recombination in DNA repair
• Mon 11/27/00: Discussion of outside reading (chromatin assembly following replication)

Note:

Some of the information presented on DNA repair mechanisms will be provided from sources other than the textbook. The relevant figures and tables will be provided as photocopies on the day when the material is presented.

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