Module 3 - DNA replication part 3

Why are base pair mismatches rare?

Complementary base pairs have much higher stability than mismatched pairs

How does configuration of the DNA polymerase active site help fidelity?

Helix distortion caused by mispairing prevents incorrect nucleotide from fittingproperly in active site

How does DNA polymerase proofread?

It uses a 3′ to 5′ exonuclease activity to digest the newly made strand until the mismatched nucleotide is removed.

How many origins of replication do eukaryotic chromosomes have?

Multiple

What is the directionality of DNA replication in eukaryotes?

DNA replication proceeds bidirectionally from many origins of replication

What are the origins of replication in Saccharomyces cerevisae termed?

autonomously replicating sequences

Where are ARSs found?

Within a nucleosome-free region (NFR)

What do origins of replication in more complex eukaryotes contain?

G-rich sequences or g4 motifs

What are the three main classes of replication origins in complex eukaryotes?

Constitutive: used all the time

Flexible: used in a random manner; most common type

Dormant: used during cell differentiation or only at a specific stage of development

How does replication begin?

With the assemply of the prereplication complex (preRC)

What is the ORC?

Origin recognition complex: a 6 subunit complex that acts as the first initiator of eukaryotic DNA replication

The arechael origin of replication is

AT-RICH

What DNA polymerases have the primary function of replicating DNA in mammalian cells?

alpha, delta, epsilon, and gamma

What are alpha, delta, and epsilon related to? (DNA type)

Nuclear DNA

What is gamma related to (DNA)?

Mitochondrial DNA

Which DNA polymerase is the only polymerase to associate with primase?

DNA polymerase alpha

What is polymerase switch:?

The exchange of DNA pol α for ε or δ , which s required for elongation of the leading and lagging strands

What are translesion-replicating polymerases?

They are involved in the replication of damaged DNA and can synthesize a complementary strand over the abnormal region.

What removes the primer in eukaryotes?

Flap endonuclease

If a flap is too long, what does it get cleaved by?

DNA2 nuclease/helicase

Linear eukaryotic chromosomes have ______ at both ends

telomeres

What are the two "unusual" features of DNA polymerases?

They synthesize DNA only in the 5' to 3' direction

They cannot initiate DNA synthesis on a bare (unprimed) DNA strand

Can strands be replicated at the 3' ends of linear chromosomes?

No

If there are replication problems at the ends of linear chromosomes, what happens?

The linear chromosome becomes progressively shorter with each round of DNA replication

What does telomerase do?

It catalyzes telomeres so they become longer and aren't affected too much by telomere erosion.

What are the three steps to enzymatic action of telomerase?

1. Binding

2. Polymerization

3. Translocation

What happens to telomeres as aging occurs?

Telomeres shorten (8k bp at birth to 1.5 k in elderly)

What happens to cells when telomeres are short?

They become senescent, which means the lose their ability to divide.

What can be done to block senescence?

Insertion of highly active telomerase cab block senescence.

What is telomerase activity like in cancer cells?

It is elevated