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Postreplication
Checkpoint
When the genomic DNA of eukaryotic cells becomes damaged by
spontaneous processes, chemical mutagens, or sunlight exposure, the
replication of damaged DNA triggers a cellular response called a
postreplication checkpoint.[1]
This response prevents cell cycle progression until postreplication repair processes
are completed, and may control the activity of these DNA repair
pathways.[2]
In cell types that execute S
phase before mitosis,
such as fission yeast and human cells, the postreplication
checkpoint makes time for repair by delaying the onset of mitosis.
In cell types where mitosis and S phase are concurrent, such as
budding yeast, the postreplication checkpoint delays the progress
of mitosis at metaphase.[3]
The chk1 gene is required to mediate the
postreplication checkpoint and is conserved in yeast and humans.
Fission yeast cells in which the chk1 gene has been
disrupted progress normally through the cell cycle after exposure
to UV radiation until they have carried damaged DNA through S-phase
and the subsequent mitosis, at which point cells begin to die and
exhibit gross chromosomal damage.[1]
The BRCA1 tumor suppressor plays a role in the activation
of human chk1,[4]
therefore the posreplication checkpoint may prevent the genetic
changes that lead to cancer.
The
Signal for Activation
A number of genes required for the postreplication checkpoint
encode proteins that recognize single-stranded DNA and the 5' end
of transitions between single-stranded DNA and double-stranded
DNA.[5][6] These
structure are known to be generated in two different ways during S
phase. The replication of DNA containing damaged bases leaves gaps
in the newly-synthesized DNA strand,[7][8] and the
replication of nicked or gapped DNA creates double-strand breaks.
Both structures are thought to activate the postreplication
checkpoint. 
References
- ^ a
b
Callegari AJ, Kelly TJ.
UV irradiation induces a postreplication DNA damage
checkpoint. Proc Natl Acad Sci U S A 2006;
103:15877-82
- ^ Callegari AJ, Kelly TJ.
Shedding light on the DNA damage checkpoint. Cell Cycle
2007; 6:660-6.
- ^
Cohen-Fix O, Koshland D. The anaphase inhibitor of
Saccharomyces cerevisiae Pds1p is a target of the DNA damage
checkpoint pathway. Proc Natl Acad Sci U S A 1997;
94:14361-6.
- ^
Yarden RI, Pardo-Reoyo S, Sgagias M, Cowan KH, Brody LC. BRCA1
regulates the G2/M checkpoint by activating Chk1 kinase upon DNA
damage. Nat Genet 2002; 30:285-9.
- ^
Ellison V, Stillman B. Biochemical characterization of DNA
damage checkpoint complexes: clamp loader and clamp complexes with
specificity for 5' recessed DNA. PLoS Biol 2003; 1:E33.
- ^
Zou L, Elledge SJ. Sensing DNA damage through ATRIP recognition
of RPA-ssDNA complexes. Science 2003; 300:1542-8.
- ^
Lehmann AR. Post-replication repair of DNA in
ultraviolet-irradiated mammalian cells. No gaps in DNA synthesized
late after ultraviolet irradiation. Eur J Biochem 1972;
31:438-45.
- ^
Lopes M, Foiani M, Sogo JM. Multiple mechanisms control
chromosome integrity after replication fork uncoupling and restart
at irreparable UV lesions. Mol Cell 2006; 21:15-27.
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