Biology Reference
In-Depth Information
in combination with an Msh2 deficiency, the amount of homeologous recom-
bination events increased.
474
RecQ helicase Werner syndrome (WRN) has also
been implicated in suppressing homeologous recombination by exhibiting
strong interaction with the MSH2-MSH6, MSH2-MSH3, and MLH1-PMS2
heterodimers.
475
To date, a reaction that suppresses homeologous recombina-
tion
in vitro
has not been developed.
XII. Conclusion
HR is mechanistically conserved in prokaryotes and eukaryotes. However,
because of the genome complexity in eukaryotes, additional mediators are
required for the successful repair of DSBs. Defective HR leads to genomic
instability and tumorigenesis. Paradoxically, unregulated HR also leads to the
same outcome. Therefore, eukaryotic cells have evolved elegant mechanisms to
regulate each step of HR to ultimately produce an accurate repair outcome.
References
1. D'Andrea AD, Grompe M. The Fanconi anaemia/BRCA pathway.
Nat Rev Cancer
2003;
3
:23-34.
2. Ellis NA, Groden J, Ye TZ, et al. The Bloom's syndrome gene product is homologous to RecQ
helicases.
Cell
1995;
83
:655-66.
3. Miki Y, Swensen J, Shattuck Eidens D, et al. A strong candidate for the breast and ovarian
cancer susceptibility gene BRCA1.
Science
1994;
266
:66-71.
4. Savitsky K, Bar Shira A, Gilad S, et al. A single ataxia telangiectasia gene with a product similar
to PI-3 kinase. [See comments].
Science
1995;
268
:1749-53.
5. Tavtigian SV, Simard J, Rommens J, et al. The complete BRCA2 gene and mutations in
chromosome 13q-linked kindreds. [See comments].
Nat Genet
1996;
12
:333-7.
6. Hoeijmakers
for preventing cancer.
Nature
JH. Genome maintenance mechanisms
2001;
411
:366-74.
7. Lobrich M, Jeggo PA. The impact of a negligent G2/M checkpoint on genomic instability and
cancer induction.
Nat Rev Cancer
2007;
7
:861-9.
8. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells
as a therapeutic strategy.
Nature
2005;
434
:917-21.
9. Zickler D, Kleckner N. Meiotic chromosomes: integrating structure and function.
Annu Rev
Genet
1999;
33
:603-754.
10. Marston AL, Amon A. Meiosis: cell-cycle controls shuffle and deal.
Nat Rev Mol Cell Biol
2004;
5
:983-97.
11. Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where we have been, where we
are going.
Hum Mol Genet
2007;
16
(Spec No. 2):R203-8.
12. Hassold T, Sherman S, Hunt PA. The origin of trisomy in humans.
Prog Clin Biol Res
1995;
393
:1-12.
13. Heyting C. Synaptonemal complexes: structure and function.
Curr Biol
1996;
8
:389-96.
