Recombination Proteins in Yeast Replication
Several replication mutants display increased levels of recombination, suggesting a link between these processes.
Certain alleles of Saccharomyces pombe DNA polymerase α, DNA ligase, and rad2+ have mutator phenotypes.
The increase in mutation frequency in these mutants suggests that the corresponding wild-type proteins prevent genome changes and rearrangements, which may result from recombination during S phase.
Recombination is elevated in mcm mutant cells that have been arrested in S phase.
In addition, S.
pombe rad2 mutants are synthetically lethal in combination with mutants of rad50, rhp51, or rhp54 (the S.
pombe homologs of RAD50, RAD51, and RAD54), suggesting that recombination functions become essential when Okazaki fragment metabolism is compromised.
The association of impaired replication function with increased recombination has also been described in S.
cerevisiae and prokaryotes, suggesting this is a general feature of S phase.
Certain recombination mutants display S phase defects.
In the S.
pombe rad50 mutant, S phase is delayed relative to wild type and the cells are sensitive to HU.
In vertebrate cells, inactivation of the recombination proteins Rad51 or Mre11 leads to DNA strand breaks and cell lethality.
These and other observations have led to the suggestion that recombination proteins are normal components of S-phase progression in eukaryotes that protect genome integrity.
Thus, replication fork stalls and starts may occur as part of normal S phase in eukaryotes, as has been described in prokaryotes.
There are several possible consequences of a stalled replication fork, which may depend on its cause.
Ideally, fork structure is protected and its components remain assembled during the arrest.
However, the fork may lose structural integrity if this protection fails, resulting in its collapse and the generation of DNA breaks; these breaks are likely to be lethal to the cell if they are not repaired.
Recombination is one mechanism that can reestablish a replication fork from a DNA break.
Although recombination-dependent replication has been best characterized in prokaryotes, there is evidence that a similar process operates in eukaryotes.
In S.
cerevisiae, break-induced replication (BIR) can replicate hundreds of kilobases of DNA starting from a chromosomal break.
In S.
pombe, cells lacking telomerase can replicate telomere sequences, presumably by a recombinational mechanism.
Importantly, replication mediated by recombination is predicted to be independent of replication origins and origin proteins.
Thus, there may be mechanistic links between recombination and replication throughout S phase which are likely to be significant for the maintenance of overall genome stability.
When cells are treated with HU, replication forks stall.
If the structure of the fork can be maintained through the arrest, then the fork may resume synthesis once HU is removed from the media.
If the fork structure cannot be maintained, the fork may collapse, generating DNA double-strand breaks.
Recombination is one mechanism that may repair DNA breaks and reestablish stalled replication forks.
Read more about S-Phase events in Mitosis cycle in yeast
Certain alleles of Saccharomyces pombe DNA polymerase α, DNA ligase, and rad2+ have mutator phenotypes.
The increase in mutation frequency in these mutants suggests that the corresponding wild-type proteins prevent genome changes and rearrangements, which may result from recombination during S phase.
Recombination is elevated in mcm mutant cells that have been arrested in S phase.
In addition, S.
pombe rad2 mutants are synthetically lethal in combination with mutants of rad50, rhp51, or rhp54 (the S.
pombe homologs of RAD50, RAD51, and RAD54), suggesting that recombination functions become essential when Okazaki fragment metabolism is compromised.
The association of impaired replication function with increased recombination has also been described in S.
cerevisiae and prokaryotes, suggesting this is a general feature of S phase.
Certain recombination mutants display S phase defects.
In the S.
pombe rad50 mutant, S phase is delayed relative to wild type and the cells are sensitive to HU.
In vertebrate cells, inactivation of the recombination proteins Rad51 or Mre11 leads to DNA strand breaks and cell lethality.
These and other observations have led to the suggestion that recombination proteins are normal components of S-phase progression in eukaryotes that protect genome integrity.
Thus, replication fork stalls and starts may occur as part of normal S phase in eukaryotes, as has been described in prokaryotes.
There are several possible consequences of a stalled replication fork, which may depend on its cause.
Ideally, fork structure is protected and its components remain assembled during the arrest.
However, the fork may lose structural integrity if this protection fails, resulting in its collapse and the generation of DNA breaks; these breaks are likely to be lethal to the cell if they are not repaired.
Recombination is one mechanism that can reestablish a replication fork from a DNA break.
Although recombination-dependent replication has been best characterized in prokaryotes, there is evidence that a similar process operates in eukaryotes.
In S.
cerevisiae, break-induced replication (BIR) can replicate hundreds of kilobases of DNA starting from a chromosomal break.
In S.
pombe, cells lacking telomerase can replicate telomere sequences, presumably by a recombinational mechanism.
Importantly, replication mediated by recombination is predicted to be independent of replication origins and origin proteins.
Thus, there may be mechanistic links between recombination and replication throughout S phase which are likely to be significant for the maintenance of overall genome stability.
When cells are treated with HU, replication forks stall.
If the structure of the fork can be maintained through the arrest, then the fork may resume synthesis once HU is removed from the media.
If the fork structure cannot be maintained, the fork may collapse, generating DNA double-strand breaks.
Recombination is one mechanism that may repair DNA breaks and reestablish stalled replication forks.
Read more about S-Phase events in Mitosis cycle in yeast
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