Introduction to Genetic Analysis 567

Introduction to - 44200_17_p545-574 10:17 AM Page 566 566 Chapter 17 Genetic Regulation of Cell Number Normal and Cancer Cells serves double duty

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serves double duty: it prevents progression of the cell cycle until the DNA damage is repaired, and, under some circumstances, it induces apoptosis. If no func- tional p53 gene is present, the cell cycle progresses even if damaged DNA has not been repaired. The progression of the cell cycle into mitosis elevates the overall fre- quency of mutations, chromosomal rearrangements, and aneuploidy and thus increases the chances that other mutations that promote cell proliferation or block apop- tosis will arise. It is now clear that null mutations able to elevate the mutation rate are important contributors to the pro- gression of tumors in humans. These null mutations are recessive mutations in tumor-suppressor genes that nor- mally function in DNA repair pathways and thus inter- fere with DNA repair. They promote tumor growth in- directly by elevating the mutation rate, which makes it much more likely that a series of oncogene and tumor- suppressor mutations will arise, corrupting the normal regulation of the cell cycle and programmed cell death. Large numbers of such tumor-suppressor-gene muta- tions have been identiFed, including some associated with heritable forms of cancer in speciFc tissues. Exam- ples are the BRCA1 and BRCA2 mutations and breast cancer. through its removal from the genome, and the location
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This note was uploaded on 01/10/2011 for the course BIOL BIOL taught by Professor Johnson during the Spring '08 term at Aberystwyth University.

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