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Replication Stress in Activated Huma...

Guilz, Nicole C.,

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Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis // Nicole C Guilz.
Author:	Guilz, Nicole C.,
Description:	1 electronic resource (153 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-07, Section: B.
Contained By:	Dissertations Abstracts International85-07B.
Subject:	Biology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30820432
ISBN:	9798381409529

Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis /
Guilz, Nicole C.,

Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis /Nicole C Guilz. - 1 electronic resource (153 pages)

Source: Dissertations Abstracts International, Volume: 85-07, Section: B.

Natural killer cells are innate immune effectors that kill virally infected or malignant cells. Natural killer cell deficiency (NKD) occurs when NK cell development or function are impaired, and individuals with NKD are susceptible to severe and recurrent viral infections. Several gene deficiencies result in NKD, including variants in MCM4, GINS1, MCM10 and GINS4, which are components of the CDC45-MCM-GINS (CMG) helicase. The CMG helicase unwinds DNA during replication and is expressed in any actively proliferating cell. NK cells are more strongly impacted by mutational deficiencies in helicase proteins than other lymphocytes, though the mechanisms underlying this susceptibility are not completely understood. NK cells from individuals with NKD as a result of helicase deficiency have increased DNA damage, cell cycle arrest, and replication stress. We found that activated NK cells undergo apoptosis and autophagy in response to this stress, unlike activated T cells. We also identified a patient with a damaging variant in CDC45 to further support these findings of the effects of replication stress on NK cells. This individual, due to broader involvement of the immune system, requires a wider definition of natural killer cell disease, termed NK IEI. However, this CDC45-deficient individual's cells display disrupted cell cycle, increased DNA damage and replication stress, with upregulation of apoptosis genes in NK cells. These findings show that sensitivity to replication stress affects human NK cell survival and function and can contribute to NK cell deficiency and human disease.

English

ISBN: 9798381409529Subjects--Topical Terms:

522710
Biology.
Subjects--Index Terms:

Natural killer cells

Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis /
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520 $a Natural killer cells are innate immune effectors that kill virally infected or malignant cells. Natural killer cell deficiency (NKD) occurs when NK cell development or function are impaired, and individuals with NKD are susceptible to severe and recurrent viral infections. Several gene deficiencies result in NKD, including variants in MCM4, GINS1, MCM10 and GINS4, which are components of the CDC45-MCM-GINS (CMG) helicase. The CMG helicase unwinds DNA during replication and is expressed in any actively proliferating cell. NK cells are more strongly impacted by mutational deficiencies in helicase proteins than other lymphocytes, though the mechanisms underlying this susceptibility are not completely understood. NK cells from individuals with NKD as a result of helicase deficiency have increased DNA damage, cell cycle arrest, and replication stress. We found that activated NK cells undergo apoptosis and autophagy in response to this stress, unlike activated T cells. We also identified a patient with a damaging variant in CDC45 to further support these findings of the effects of replication stress on NK cells. This individual, due to broader involvement of the immune system, requires a wider definition of natural killer cell disease, termed NK IEI. However, this CDC45-deficient individual's cells display disrupted cell cycle, increased DNA damage and replication stress, with upregulation of apoptosis genes in NK cells. These findings show that sensitivity to replication stress affects human NK cell survival and function and can contribute to NK cell deficiency and human disease.
546 $a English
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650 4 $a Biology. $3 522710
650 4 $a Immunology. $3 611031
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653 $a Immune effectors
653 $a Apoptosis genes
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