DNA Repair and Recombination

Mutations are Changes to the DNA Sequences

-They can occur in: ___ and ___

germ and somatic

Which mutations are heritable?

-Germ cells are cells that give rise to reproductive cells like eggs and sperm

-__ cells are non-germ cells

Somatic

When the DNA replication machinery fails, the cell has a backup mechanism called __

DNA repair

Repair corrects __% of the mistakes made by DNA replication, making the overall error rate 1 in __ nucleotides

99 : 10^9

DNA Repair includes:

-__&__ repair. Includes single strand break repair

-__ repair

-Base excision & nucleotide excision

-Double strand break

Mutations are introduced (__) if they are not corrected before the next round of replication. Fixed = “set” not “repaired”

fixed

3 Possibilities once an error is made:

-__: Permanent mutation in one strand or Template strand is uncharged

-“Repair: of __ strand only: “Repair” of the templates strand will lead to mutation in both strands

-Repair of __ strand: Error is corrected or Mutation prevented

-No repair

-template

-new

Therefore, mutation are only prevented is they are corrected in the __ strand before the next round of replication

NEW

Mechanism for Repair Involves 3 steps (Summary)

-__: Mistakes are recognized by specialized enzymes. A nuclease removes the mistakes, leaving a small gap

-__: The gap is filled by DNA polymerase (see also digestion of RNA primers)

-__: Ligase will seal up gap between the newly synthesized DNA (repaired) with existing strand

-Excision

-Resynthesis

-Ligation

When both strands of the DNA are damaged repair is difficult because of the lack of proper __ to use as guide

-Double strand breaks require special repair mechanisms: 

• Non-homologous __

• Homologous __

template

• end-joining

• recombination

Non-homologous end-joining:

-Ligates the broken strands back together

-Typically a few nucleotides at the break points are lost

-Easy but prone to introduce __

• What can happen?

• Shift in __!

-mutations

• reading frame

Homologous Recombination: A more complex mechanism & Required the presence of a homologous chromosome (extensive region of identity is needed)

-What is a homologous pair of chromosome?

• Pair of the same chromosomes

• But each is from a different parent

• For example: Each human carried 1 chromosome #14 from the mother, and 1 chromosome #14 from the father

  • The two chromosomes 14’2 are __ to each other

• parent

  • homologous

1. Step 1 of Homologous Recombination:

-__ and pairing of homologous chromosomes occurs

• Orange=mom

• red=dad

Double strand breaks

Step 2 of Homologous Recombination:

-Digestion of broken ends by a __

-Necessary to “attack” the __ DNA duplex

-nuclease

-homologous

Step 3 of Homologous Recombination:

-__. One strand of DNA pairs with a strand from the homologous chromosome

-Strand invasion

Step 4 of Homologous Recombination:

-__ DNA is synthesized using complementary strand of the homologous chromosome

New

Step 5 of Homologous Recombination:

-The __ can migrate as new DNA is synthesized

-branch point

Step 6 of Homologous Recombination:

-__ seals up the DNA strands

-All that is needed for this repair mechanism is another intact __!

-Ligation

-chromosome

Creating the ____:

-Stage where the 4 strands of DNA from two __ chromosomes are partially paired with each other

• DNA Junction

• DNA cross? NO! —-

Holiday Junction

-homologous