Normal cells age and die and are replaced in a controlled and orderly manner by

Normal cells age and die and are replaced in a

This preview shows page 7 - 9 out of 17 pages.

• Normal cells age and die, and are replaced in a controlled and orderly manner by new cells. Apoptosis is the normal, programmed death of cells. Normal cells can divide only about fifty times before they die. This is related to their ability to replicate DNA only a limited number of times. Each time the chromosome replicates, the ends (telomeres) shorten. In growing cells, the enzyme telomerase replaces these lost ends. Adult cells lack telomerase, limiting the number of times the cell can divide. However, telomerase is activated in cancer cells, allowing an unlimited number of cell divisions. • Normal cells cease to divide and die when there is DNA damage or when cell division is abnormal. Cancer cells continue to divide, even when there is a large amount of damage to DNA or when the cells are abnormal. These progeny cancer cells contain the abnormal DNA; so, as the cancer cells continue to divide they accumulate even more damaged DNA. Structure The Multiple Changes Needed for a Cell to Become Cancerous As noted above, there are many differences between normal cells and cancer cells. Also noteworthy is the number of “checkpoints” that need to be bypassed for a cell to become cancerous. The cell needs to have growth factors that prompt it to grow even when growth is not necessary. They have to evade proteins that direct cells to stop growing and die when they become abnormal. The cell needs to evade signals from other cells, The cells need to lose the normal “stickiness” (adhesion molecules) that normal cells produce. Mutation of the cysteine residues that coordinate the Zn2+ atoms have been reported as clinically important, indicating that they result in altered function and an increased risk of cancer. Mutation of residues in Site I result in altered folding of the RING domain. A more complete study of Site II residue mutations found altered structure by mass spectrometry and reduced Zn2+ binding at Site II. This study reported that BRCA1/BARD1 heterodimerization was not affected by Site II mutations, however a later study by the same group reported that several Site I and Site II mutations caused not only a decrease in ubiquitin ligase activity, but also a decrease in co-immunoprecipitation of BRCA1 and BARD1 [29]. These studies suggest that mutation of Site I and Site II residues may affect BRCA1 ubiquitin ligase activity by either decreasing BRCA1/BARD1 heterodimerization or BRCA1/UbcH5 interaction. Another study has
Image of page 7
shown that the E3-ubiquitin ligase activity of BRCA1 is inhibited by platinum (Pt)-based alkylating chemotherapeutic drugs. Cisplatin forms adducts through its Pt atom with His117 of BRCA1, causing conformational changes and inhibiting the E3-ubiquitin ligase activity in vitro. Other Pt-based drugs had similar functional effects. Transplatin, carboplatin and oxaliplatin all reduced the E3 ligase activity of BRCA1 at therapeutically relevant concentrations. The large number of RING domain mutations that
Image of page 8
Image of page 9

You've reached the end of your free preview.

Want to read all 17 pages?

  • Fall '17
  • DR. MOSLEY

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern

Stuck? We have tutors online 24/7 who can help you get unstuck.
A+ icon
Ask Expert Tutors You can ask You can ask ( soon) You can ask (will expire )
Answers in as fast as 15 minutes
A+ icon
Ask Expert Tutors