NOTES: Ch. 16 (part 2) – DNA Replication and Repair
● During DNA replication, base-pairing enables existing (“parental”) DNA strands to
for new (“daughter”) complementary strands
 Watson and Crick proposed that during DNA replication:
1)
;
2) each strand is a template for assembling a
;
3)
;
4)
link the nucleotides together at their sugar-phosphate groups.
 Watson and Crick’s proposed model is a
will have
model (each of the 2 daughter molecules
from the parent molecule and 1 newly created strand)
 DNA replication begins at special sites called
.
-DNA double helix opens at the origin & replication “forks” spread in both directions
away from the central initiation site creating a
.
-100’s to 1000’s of replication origins form in eukaryotic chromosomes, which
eventually fuse forming 2 continuous DNA molecules
“Unzipping” the parent DNA strands:
 2 types of proteins involved with separation of parental DNA strands:
*HELICASES: enzymes that catalyze
template
to expose
*single-strand binding proteins:
unwound DNA until new strands can be made
& stabilize
Elongating the new DNA strands:
-new nucleotides align themselves along templates of old DNA strands according to base-pairing rules (A-T, G-C)
DNA polymerases catalyze synthesis of new DNA strand:
-DNA polymerase links the nucleotides to the growing strand;
; new nucleotides are added only to the 3’ end of the
growing strand
What is the source of energy that drives the synthesis of the new DNA strands?
● Nucleoside triphosphates (nucleotides with 3 phosphate groups linked to the 5’ carbon of the sugar)
-nucleoside triphosphate loses
-exergonic hydrolysis of these phosphate bonds drives the endergonic synthesis of DNA; it provides
the energy to form new covalent linkages between nucleotides
Now, back to…DNA polymerase can only add on the 3’ end!
*RECALL: DNA strands run in opposite directions; DNA polymerase can elongate strands only in the 5’ to
3’ direction
 this problem is solved by
of 1 strand (
of the complementary strand (
) and…
)
 the LAGGING STRAND is produced as a series of short fragments (
) which
are synthesized in the 5’ to 3’ direction and then linked together by the enzyme
.
 Before new DNA strands can form, there must be small pre-existing
to start the
addition of new nucleotides
-a primer is a
.
-primers are polymerized
*only 1 primer is necessary for replication of the leading strand, but many primers are necessary to
replicate the lagging strand
.
*an RNA primer must intitate the synthesis of each
*DNA polymerase removes the RNA primer and replaces it with DNA bases.
Enzymes proofread DNA during its replication and repair damage to existing DNA
 MISMATCH REPAIR:
*one form of colon cancer is due to a defect in one of the proteins involved in this type of DNA repair
 NUCLEOTIDE EXCISION REPAIR:
-an enzyme (
-enzymes
) cuts out damaged segment of DNA
and
fill in the resulting gaps
*xeroderma pigmentosum is caused by an inherited defect in an excision-repair enzyme
What about the 5’ ends of long DNA molecules?
 DNA polymerase can only add nucleotides to the 3’ end of a preexisting polynucleotide…
 The usual replication machinery provides no way to complete the 5’ ends of daughter DNA strands;
 As a result, repeated rounds of replication produce
Solutions to the problem:
 Prokaryotes avoid this problem by having circular DNA molecules…but what about eukaryotes?
 The answer is…
!
TELOMERES:
 special nucleotide sequences at the end of eukaryotic chromosomal DNA molecules;

;
 contain multiple repetitions of one short nucleotide sequence
 example:
.
 # of repeats varies be
.

;
 they protect an organism’s genes from being eroded through successive rounds of DNA replication.
 a special enzyme,
, catalyzes the lengthening of telomeres
Things that make you go hmmmm…
 telomerase is NOT present in most cells of multicellular organisms (like ourselves!)…this means…
 the DNA of dividing somatic cells tends to be shorter in older individuals (older tissues / cells);
 thus, telomeres may be a limiting factor in the life span of certain tissues and even the organism as a whole…
 telomerase has been found, however, in somatic cells that are
! Wow!…right?