• Research advances understanding of DNA r

    From ScienceDaily@1:317/3 to All on Tuesday, March 08, 2022 21:30:40
    Research advances understanding of DNA repair

    Date:
    March 8, 2022
    Source:
    Florida State University
    Summary:
    A researcher has made a discovery that alters our understanding
    of how the body's DNA repair process works and may lead to new
    chemotherapy treatments for cancer and other disorders. Researchers
    discovered that base excision repair has a built-in mechanism to
    increase its effectiveness -- it just needs to be captured at a
    very precise point in the cell life cycle.



    FULL STORY ==========================================================================
    A Florida State University College of Medicine researcher has made a
    discovery that alters our understanding of how the body's DNA repair
    process works and may lead to new chemotherapy treatments for cancer
    and other disorders.


    ==========================================================================
    The fact that DNA can be repaired after it has been damaged is one of
    the great mysteries of medical science, but pathways involved in the
    repair process vary during different stages of the cell life cycle. In
    one of the repair pathways known as base excision repair (BER), the
    damaged material is removed, and a combination of proteins and enzymes
    work together to create DNA to fill in and then seal the gaps.

    Led by Eminent Professor Zucai Suo, FSU researchers discovered that BER
    has a built-in mechanism to increase its effectiveness -- it just needs
    to be captured at a very precise point in the cell life cycle.

    The study appears in the current issue of Proceedings of the National
    Academy of Sciences.

    In BER, an enzyme called polymerase beta (PolyB) fulfills two functions:
    It creates DNA, and it initiates a reaction to clean up the leftover
    "chemical junk." Through five years of study, Suo's team learned that by capturing PolyB when it is naturally cross-linked with DNA, the enzyme
    will create new genetic material at a speed 17 times faster than when
    the two are not cross-linked.

    This suggests that the two functions of PolyB are interlocked, not
    independent, during BER.

    The research improves the understanding of cellular genomic stability,
    drug efficacy and resistance associated with chemotherapy.



    ========================================================================== "Cancer cells replicate at high speed, and their DNA endures a lot of
    damage," Suo said. "When a doctor uses certain drugs to attack cancer
    cells' DNA, the cancer cells must cope with additional DNA damage. If
    the cancer cells cannot rapidly fix DNA damage, they will die. Otherwise,
    the cancer cells survive, and drug resistance appears.

    This research examined naturally cross-linked PolyB and DNA, unlike
    previous research that mimicked the process. Prior to this study,
    researchers had identified the enzymes involved in BER but didn't fully understand how they work together.

    "When we have nicks in DNA, bad things can happen, like the double strand breaking in DNA," said Thomas Spratt, a professor of biochemistry and
    molecular biology at Penn State University College of Medicine who was not
    a part of the research team. "What Zucai found provides us with something
    we didn't understand before, and he used many different methods to reach
    his findings." In addition to revealing PolyB's functional dynamics,
    the team proposed a modified BER pathway and is testing the pathway in
    human cells.

    "We have been able to dig deeper into a fundamental pathway for which
    the pioneer Tomas Lindahl shared the Nobel Prize in Chemistry in 2015,"
    Suo said.

    Suo began the research as a professor of biochemistry at The Ohio State University, but the main body of work was performed since his arrival
    at FSU.

    Co-authors are Adarsh Kumar, a former postdoctoral researcher in the
    FSU College of Medicine Department of Biomedical Sciences; OSU graduate students Andrew J. Reed and Walter J. Zahurancik; and Sasha M. Daskalova
    and Sidney M.

    Hecht with the BioDesign Center for BioEnergetics and School of Molecular Sciences at Arizona State University.

    The research was supported by the National Institutes of Health under
    award number R01GM122093.


    ========================================================================== Story Source: Materials provided by Florida_State_University. Original
    written by Audrey Post. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Adarsh Kumar, Andrew J. Reed, Walter J. Zahurancik, Sasha
    M. Daskalova,
    Sidney M. Hecht, Zucai Suo. Interlocking activities of DNA
    polymerase b in the base excision repair pathway. Proceedings
    of the National Academy of Sciences, 2022; 119 (10) DOI:
    10.1073/pnas.2118940119 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220308155623.htm

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