Bibliography

Books

Friftdberg E.C., Walker G.C., and Siede IV. 1995. DNA repair and mutagenesis. ASM Press, Washington, D.C.

Kornberg A. and Baker T.A. 1992. DNA replication. 2nd edition. W. H. Freeman, N.Y.

Replication Errors and Their Repair

Lindahl T. and Wood R.D. 1999. Quality control by DNA repair. Science286: 1897-1905.

DNA Damage

Singer B. and Kusmierek J.T. 1982. Chemical mutagenesis. Amur. Rev. Biochem. 52: (555-693.

Repair of DNA Damage

Bridges B.A. 1999. DNA repair: Polymerases for passing lesions. Curr. Biol. 9: R475-R477.

Citterio E., Vermeulen W., and Hoeij makers f.H. 2000. Transcriptional healing. Cell 101: 447-450.

de Laat W.L., Jaspers N.G., and Hoeijmakers J.H. 1999. Molecular mechanism of excision nucleotide repair. Genes Dev. 13: 768-785.

Drapkin R., Reardon J.T., Ansari A., Huang J.C., Zawel L., Ahn K., Sancar A., and Reinborg [3. 1994. Dual role of TFIIH in DNA excision repair and in transcription by RNA Polymerase ft. Nature 368: 769-772.

Kleczkowska H.E., Marra G., Letiieri T., and Jiricny |. 2001. hMSH3 and hMSHti interact with PCNA and coloealize with it to replication foci. Genes and Development 15: 724-736.

Homologous Recombination at the Molecular Level

All DNA is recombinant DNA, Genetic exchange works constantly to blenrl and rearrange chromosomes, most obviously during meiusis, when homologous chromosomes pair prior to the first nuclear division. During this pairing, genetic exchange between the chromosomes occurs. This exchange, classically termed crossing over, is one of the results of homologous recombination. This recombination involves the physical exchange of DNA sequences between the: chromosomes. The frequency of crossing over between two genes on Lhe same chromosome depends on the physical distance between these genes, with long distances giving the highest frequencies of exchange. In feet, genetic maps derived from early measurements of crossing over frequencies gave the first real information about chromosome structure by revealing that genes are arranged in a fixed, linear order.

Sometimes, however, gene order does change: for example, movable DNA segments called transposons occasionally "jump" around chromosomes and promote DNA rearrangements, thus altering chromosomal organization. The recombination mechanisms responsible for transposition and other genome rearrangements are distinct from those of homologous recombination. These mechanisms are discussed in detail in Chapter 11.

Homologous recombination is an essential cellular process catalyzed by enzymes synthesized and regulated for this purpose. Besides providing genetic variation, recombination allows cells to retrieve sequences lost through DNA damage by replacing the damaged section with an undamaged DNA strand horn a homologous chromosome. Recombination also provides a mechanism to restart stalled or damaged replication forks. Furthermore, special types of recombination regulate the expression of some genes. For example, by switching specific segments within chromosomes, cells can put otherwise dormant genes into sites where: they are expressed.

In addition to providing an explanation for genetic processes, elucidating the molecular mechanisms of recombination has led to the development of methods to manipulate genes. It is, for example, now routine to generate "knock-out" and "transgenic" variants in many different experimental organisms (see Chapter 21). These methods for deleting and introducing genes within the context of a whole organism rely on recombination and are exceedingly powerful for determining gene function.

OUTLINE *

Models for Homologous Recombination

Homologous Recombination Protein

Homologous Recombination in Eukaryntes

Genetic Consequences of the Mechanism of Homologous Recombination (p. 288)

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