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The CYLD-PARP1 feedback loop regulates DNA damage repair and chemosensitivity in breast cancer cells.
Proc Natl Acad Sci U S A
January 2025
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Department of Biochemistry and Molecular Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
Poly(ADP-ribose) polymerase 1 (PARP1) plays a crucial role in DNA repair and genomic stability maintenance. However, the regulatory mechanisms governing PARP1 activity, particularly through deubiquitination, remain poorly elucidated. Using a deubiquitinase (DUB) library binding screen, we identified cylindromatosis (CYLD) as a bona fide DUB for PARP1 in breast cancer cells.
View Article and Find Full Text PDFTranscription as a double-edged sword in genome maintenance.
FEBS Lett
December 2024
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Genome maintenance is essential for the integrity of the genetic blueprint, of which only a small fraction is transcribed in higher eukaryotes. DNA lesions occurring in the transcribed genome trigger transcription pausing and transcription-coupled DNA repair. There are two major transcription-coupled DNA repair pathways.
View Article and Find Full Text PDFLAP2α orchestrates alternative lengthening of telomeres suppression through telomeric heterochromatin regulation with HDAC1: unveiling a potential therapeutic target.
Cell Death Dis
October 2024
The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Genetics, School of Basic Medical Science, Institute of Prosthodontics School and Hospital of Stomatology, General Hospital, Tianjin Medical University, 300070, Tianjin, P. R. China.
In response to the challenge of telomere attrition during DNA replication, cancer cells predominantly employ telomerase or, in 10-15% of cases, the alternative lengthening of telomeres (ALT). The intricate details of ALT, however, remain elusive. In this study, we unveil that the knockdown of lamina-associated polypeptide 2 alpha (LAP2α) in ALT cells results in telomere dysfunction, triggering a notable increase in ALT-associated hallmarks, including high frequencies of PML bodies (APBs), C-rich extrachromosomal circles (C-circles), and telomere sister chromatid exchange (T-SCE).
View Article and Find Full Text PDFRegulation of the SOS response and homologous recombination by an integrative and conjugative element.
bioRxiv
October 2024
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA.
Integrative and conjugative elements (ICEs) are mobile genetic elements that transfer between bacteria and influence host physiology and promote evolution. ICE of modulates the host DNA damage response by reducing RecA filament formation. We found that the two ICE-encoded proteins, RamT and RamA that modulate the SOS response in donors also function in recipient cells to inhibit both the SOS response and homologous recombination following transfer of the element.
View Article and Find Full Text PDFExploring Molecular Drivers of PARPi Resistance in BRCA1-Deficient Ovarian Cancer: The Role of LY6E and Immunomodulation.
Int J Mol Sci
September 2024
Department of Pathology, City of Hope, Duarte, CA 91010, USA.
Approximately 50% of patients diagnosed with ovarian cancer harbor tumors with mutations in BRCA1, BRCA2, or other genes involved in homologous recombination repair (HR). The presence of homologous recombination deficiency (HRD) is an approved biomarker for poly-ADP-ribose polymerase inhibitors (PARPis) as a maintenance treatment following a positive response to initial platinum-based chemotherapy. Despite this treatment option, the development of resistance to PARPis is common among recurrent disease patients, leading to a poor prognosis.
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