A slippage event normally occurs when a sequence of repetitive nucleotides (tandem repeats) are found at the site of replication. When DNA polymerase encounters a direct repeat, it can undergo a replication slippage. Strand slippage may also occur during the DNA synthesis step of DNA repair processes.

How can a replication error be corrected?

Errors during Replication. Most of the mistakes during DNA replication are promptly corrected by DNA polymerase which proofreads the base that has just been added. In proofreading, the DNA pol reads the newly-added base before adding the next one so a correction can be made.

What is DNA replication slippage?

Replication slippage or slipped-strand mispairing involves the misalignment of DNA strands during the replication of repeated DNA sequences, and can lead to genetic rearrangements such as microsatellite instability.

How do you fix Depurination?

Depurination, which is by far the most frequent type of damage suffered by DNA, also leaves a deoxyribose sugar with a missing base. Depurinations are directly repaired beginning with AP endonuclease, following the bottom half of the pathway in Figure 5-50A.

How is replication slippage fixed?

When slippage takes place, the presence of nearby duplicate bases stabilizes the slippage so that replication can proceed. During the next round of replication, when the two strands separate, the insertion or deletion on either the template or primer strand, respectively, will be perpetuated as a permanent mutation.

What is a slipped structure?

Slipped strand DNA structures are formed when complementary strands comprising direct repeats pair in a misaligned, or slipped, fashion along the DNA helix axis.

What is replication repair?

Post replication repair is a mechanism specialized in tolerating lesions in single stranded template. DNA replication is a multistep process with two key events; (1) unwinding of the annealed double helix to expose ssDNA and (2) using this ssDNA as template to synthesize daughter strands.

Can cells fix mistakes in DNA replication?

Fortunately, cells have evolved highly sophisticated means of fixing most, but not all, of those mistakes. Some of the mistakes are corrected immediately during replication through a process known as proofreading, and some are corrected after replication in a process called mismatch repair.

What is the difference between depurination and deamination?

Depurination; the hydrolytic removal of guanine or adenine from the #1 C (carbon) of deoxyribose in a DNA strand. Deamination: hydrolytic removal of amino (-NH2) groups from guanine (most common), cytosine or adenine. Oxidative damage of deoxyribose with any base, but most commonly purines.

How can DNA be repaired?

Most damage to DNA is repaired by removal of the damaged bases followed by resynthesis of the excised region. Some lesions in DNA, however, can be repaired by direct reversal of the damage, which may be a more efficient way of dealing with specific types of DNA damage that occur frequently.

How do DNA repair enzymes work?

DNA repair enzymes are enzymes that recognize and correct physical damage in DNA, caused by exposure to radiation, UV light or reactive oxygen species. The correction of DNA damage alleviates loss of genetic information, generation of double-strand breaks, and DNA crosslinkages.

How are slippage errors repaired in DNA replication?

Replication slippage errors should be repaired by the DNA mismatch repair pathway (see Fig. 35-2 ). Individuals with expanded repeats are fully proficient in DNA mismatch repair; thus, slippage events should be repaired.

What are the predictions of the replication slippage model?

The replication slippage model makes two major predictions. First, as DNA replication is linked to the cell cycle, expansion should be a cell-cycle-dependent event. Second, slippage products must escape mismatch repair to become fixed as mutations (see Fig. 35-2 ).

What happens during polymerase slippage during replication?

During replication (b) polymerase slippage may occur, leading to a loop out on the either the daughter strand (c) or the template strand (j). Both slipped-strand structures should be recognized by the DNA mismatch repair pathway (d, k) and the error corrected (e, 1), resulting in no net length change (f, m).

How does slippage cause variation in microsatellites?

Replication slippage is known to cause variation of a few repeat units in microsatellites due to a local misalignment of the template and nascent strands during a brief detachment of the DNA polymerase (Levinson and Gutman, 1987 Schloetterer and Tautz, 1992 ).