ORCID

https://orcid.org/0000-0002-0584-5462

Date of Award

8-14-2023

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Biochemistry)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

MYSM1 deficiency has been identified in patients with B cell lymphopenia, hypogammaglobulinemia, primary immune deficiency and bone marrow failure. MYSM1 is a known deubiquitinase that acts on histone H2A to promote gene expression. MYSM1 also functions in cellular responses to DNA injury and patients with loss of MYSM1 have increased sensitivity to DNA damaging agents. The specific role and function of MYSM1 in DNA damage responses has yet to be determined. Here, I have shown that MYSM1 does not mediate generation or repair of DSBs, but rather acts to attenuate and terminate DNA damage signaling after repair. Loss of MYSM1 results in persistent DNA damage response signaling characterized by persistent 53BP1 foci and ATM activity, whereas MYSM1 overexpression results in premature DDR resolution without break repair. These results demonstrate that MYSM1 plays an important role in the resolution of DDR signaling, a vital component of genomic integrity and lymphocytic development.

Language

English (en)

Chair and Committee

Jeffrey Bednarski

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Included in

Biochemistry Commons

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