FAM111A protects replication forks from protein obstacles via its trypsin-like domain.

Camptothecin / pharmacology Cell Cycle Checkpoints / drug effects Cell Line, Tumor DNA Damage DNA Replication DNA Topoisomerases, Type I / metabolism DNA, Single-Stranded / metabolism Humans Mutation / genetics Poly(ADP-ribose) Polymerase Inhibitors / pharmacology Poly(ADP-ribose) Polymerases / metabolism Protein Binding / drug effects Protein Domains Receptors, Virus / chemistry Trypsin / chemistry

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
12 03 2020
Historique:
received: 28 08 2019
accepted: 24 02 2020
entrez: 14 3 2020
pubmed: 14 3 2020
medline: 7 7 2020
Statut: epublish

Résumé

Persistent protein obstacles on genomic DNA, such as DNA-protein crosslinks (DPCs) and tight nucleoprotein complexes, can block replication forks. DPCs can be removed by the proteolytic activities of the metalloprotease SPRTN or the proteasome in a replication-coupled manner; however, additional proteolytic mechanisms may exist to cope with the diversity of protein obstacles. Here, we show that FAM111A, a PCNA-interacting protein, plays an important role in mitigating the effect of protein obstacles on replication forks. This function of FAM111A requires an intact trypsin-like protease domain, the PCNA interaction, and the DNA-binding domain that is necessary for protease activity in vivo. FAM111A, but not SPRTN, protects replication forks from stalling at poly(ADP-ribose) polymerase 1 (PARP1)-DNA complexes trapped by PARP inhibitors, thereby promoting cell survival after drug treatment. Altogether, our findings reveal a role of FAM111A in overcoming protein obstacles to replication forks, shedding light on cellular responses to anti-cancer therapies.

Identifiants

DOI: 10.1038/s41467-020-15170-7 PMID: 32165630 PMC: PMC7067828
pubmed: 32165630
doi: 10.1038/s41467-020-15170-7
pii: 10.1038/s41467-020-15170-7
pmc: PMC7067828
doi:

Substances chimiques

DNA, Single-Stranded 0
FAM111A protein, human 0
Poly(ADP-ribose) Polymerase Inhibitors 0
Receptors, Virus 0
Poly(ADP-ribose) Polymerases EC 2.4.2.30
Trypsin EC 3.4.21.4
DNA Topoisomerases, Type I EC 5.99.1.2
Camptothecin XT3Z54Z28A

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1318

Subventions

Organisme : NCI NIH HHS
ID : R01 CA233700
Pays : United States

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Auteurs

Yusuke Kojima (Y)

Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.

Yuka Machida (Y)

Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.

Sowmiya Palani (S)

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905, USA.

Thomas R Caulfield (TR)

Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.
ORCID: 0000-0002-1055-3069

Evette S Radisky (ES)

Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA.

Scott H Kaufmann (SH)

Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
ORCID: 0000-0002-4900-7145

Yuichi J Machida (YJ)

Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. machida.yuichi@mayo.edu.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA. machida.yuichi@mayo.edu.

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Classifications MeSH

questionsmedicales.fr › Composés hétérocycliques › Alcaloïdes › Camptothécine › FAM111A protects replication forks from...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Cycle cellulaire › Points de contrôle du cycle cellulaire › FAM111A protects replication forks from...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › FAM111A protects replication forks from...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › FAM111A protects replication forks from...
questionsmedicales.fr › Phénomènes génétiques › Réplication de l'ADN › FAM111A protects replication forks from...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines liant le poly-adp-ribose › ADN topoisomérases de type I › FAM111A protects replication forks from...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › ADN simple brin › FAM111A protects replication forks from...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › FAM111A protects replication forks from...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › FAM111A protects replication forks from...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Inhibiteurs de poly(ADP-ribose) polymérases › FAM111A protects replication forks from...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Glycosyltransferase › Pentosyltransferases › ADP ribose transferases › Poly(ADP-ribose) polymerases › FAM111A protects replication forks from...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › FAM111A protects replication forks from...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Structure tertiaire des protéines › Domaines protéiques › FAM111A protects replication forks from...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs viraux › FAM111A protects replication forks from...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › Trypsine › FAM111A protects replication forks from...