The Mutatability & Repair of DNA Pt II

Mutations are also caused by compounds that substitute for normal bases, _____ ______, or slip between the bases _______ _______ to cause errors in replication.

Base analogs are structurally similar to ______ bases but differ in ways that make them _______ to the cell.

Base analogs are similar enough to _______ bases to get taken up by cells, converted into ______ _______, and incorporated into ______ during replication. But, because of the structural differences between these analogs and ______ bases, the analogs will _____ _____ innaccurately, leading to frequent _____ during the rep process.

One of the most mutagenic base analogs is __________, an analog of _______. The presence of the _____ substituent allows the base to mispair with ______ via the ___ tautomer as opposed to the _____ tautomer which is highly favored for ______ not ______

______ ______ are flat molecules containing several polycyclic rings that bind to the equally flat _____ or _______ bases of DNA, just as the bases bind or stack with each other in the _____ _____.

Intercalating agents, such as _______, _______, and ______, cause the deletion or addition of a base pair or even a few base pairs. When such deletions or additions arise in a gene, they can have profound consequences on the ________ of its mRNA because they shift the _____ ______ out of its proper reading frame.

How do intercalating agents cause short insertions and deletions?

In the case of deletions, the distortion to the _____ caused by the presence of an ______ molecule might cause the polymerase to skip a nucleotide

Some kinds of damage, such as _______ ______ or ______ and breaks in the DNA backbone, create impediments to ________ or _________. Other kinds of damage create ______ ______ that have no immediate structural consequence on replication but cause _______; these can result in a permanent alteration to the DNA sequence after _______.

State an example of the previous card

In the most direct repair mechanism, a ____ ____ simply reverses/undoes the damage. A more elaborate system is ______ _____, in which the damaged nucleotide is not repaired but removed from the DNA .

In excision repair system, the other undamaged, strand serves as a _______ for reincorporation of the correct nucleotide by _____ _______. What are the two types of excision repair

The level beyond excision repair would be ______ _____, which is used when _____ ______ are damaged, as when the DNA is broken. In such situations, one strad cannot serve as a template for the repair of the other. Hence, in _____ _____ _____ repair, sequence information is retrieved from a _____ ______ copy of the chromosome.

When Damaged bases block progression of a replicating DNA polyerase, a special ______ _____ copies across the site of the damage in a manner that dos not depend on base pairing between the ______ and newly synthesized DNA strands.

Recombinational repair is a mechanism is an example of DNA ______ ______, a system of last resort because translesion synthesis is inevitably error-prone (mutagentic)

An example of repair by simple reversal of damage is _______ which directly reverses the formation of ______ _____ that result from ______ ______.

In photoreactivation, the enzyme _____ ______ captures energy from light and uses it to break the ______ _____ linking adjacent ________. In other words, the damaged bases are mended _______.

Another example of direct reversal is the removal of the _____ _____ from the methylated base O6-methylguanine. In this case, a ________ removes the methyl group from the _______ residue by transferring it to one of its own _______ residues. This is costly to the cell because the ________ is not catalytic; having once accepted a _____ _____ it cannot be used again.

Ligation

The most prevalent way in which DNA is cleansed of damaged bases is by repair systems that ______ & ______ the altered bases. The Two principal repair systems are ______ ______ ______ & _______ _____ ______

The base excision repair, an enzyme called a _______ recognizes and removes the damaged base by _______ the _______ bond.

The resulting ______ sugar is removed from the DNA _______ in a further endonucleolytic step.

________ _______ also removes apurinic and apyrimidinic sugars that arise by ______ ______. After the damaged nucleotide has been entirely removed from the backbone, a _____ _____ _______ and  _____ ______ restore an intact strand using the undamaged strand as a ________.

DNA glycosylases are ______ specific and cells have multiple DNA glycosylases with different specificities. Thus, a specific glycosylase recognizes _____ (generated as a consequence of _______ of cytosine), and another is responsible for removing _______ (generated as a consequence of _______ of guanine). A total of ____ different DNA glycosylases have been identified in human cells.

Why is cleansing the genome of damaged bases is a formidable problem?

How is this problem resolved?

OxoG has a tendency to mispair with ______, what is the fail safe system?

Thymine adjacent to a guanine can result in mismatching by spontaneous _______ of 5-methylcytosine. Because both T and G are normal bases, how can the cell recognize the incorrect base?

Unlike base excision repair, the ______ _____ ______ enzymes do not recognize any particular ______. Rather, this system works by recognizing _______ to the shape of the double helix, such as those caused by a _____ _____ or by the presence of a bulky ______ _____ on a base

Distortions on DNA trigger a chain of events that lead to the removal of a short _____ strand segment or a ______ that includes the _____. This removal creates a _____ ____ gap which is filled in by _____ _____ using the undamaged strand as a ______ and thereby restoring he original nucleotide sequence

Nucleotide excision repair in E. coli is largely accomplished by four proteins, name them

Nucleotide excision repair story

The process of nucleotide excision repair is similar in both higher cell organisms and ______. However, machinery for detecting, excising, and repairing the damage is more complicated, involving ____ or more polypeptides.

Excision repair uses the _______ DNA strand as a template to replace a _______ segment of DNA on the other strand.

How do cells repair double strand breaksin DNA in which both strands of the duplex are broken?

DNA recombination also helps to _____ ____ in DNA replication. Consider a replication fork encounters a lesion in DNA (such as a ______ ______) that has not been corrected by NER. The DNA polymerase will sometimes stall attempting to replicate over the _____.

A DSB is the most ______ of all kinds of DNA damage. If left unmended, a DNA break can have multiple deleterious consequences, such as ______ _______ and causing _______ loss. Name two results of this

Cells typically have multiple ______ pathways for coping with DNA damage so recombination is not the only option for mending DSBs.

In yeast cells, recombination based DSB repair is the ______ pathway by which breaks are mended.

What happens early in the cell cycle before two sister chromosomes have been generated by DNA replication and a still unreplicated chromosome suffers a break?

If it is to early in the cell cycle and a DSB occurs before sister chromosomes have been generated, what is an alternative DSB repair system

NHEJ is a ______ pathway in yeast, but in higher cells, it is the ______ pathway  by which breaks are repaired

The machinery for performing NHEJ ______ and _______ the broken ends and then joins them back together. Because sequence info is lost from the ____ ____, the original sequence across the break is not ______ restored during NHEJ. Thus NHEJ is ______.

T or F The mutagenic consequences of NHEJ are far less worse than the consequences of leaving the broken DNA unrepaired.
True False

NHEJ does not involve extensive stretches of homologous sequences. Instead, the two ends of the broken DNA are joined to each other by _________ between single strands protruding from the _____ _____. It is caused by pairing of ________ ______. ______ remove single strand tails, and ____ ______ fills in the gaps

NHEJ is ubiquitous in _____ organisms and less frequent in ______ organisms

Given this info, how does non-homologous end joining and random recombination play in?

Ubiquitination