Universität zu Köln

Boehm, Stefanie, Szakal, Barnabas ORCID: 0000-0001-6888-1383, Herken, Benjamin W., Sullivan, Meghan R., Mihalevic, Michael J., Kabbinavar, Faiz F., Branzei, Dana ORCID: 0000-0002-0544-4888, Clark, Nathan L. and Bernstein, Kara A. (2016). The Budding Yeast Ubiquitin Protease Ubp7 Is a Novel Component Involved in S Phase Progression. J. Biol. Chem., 291 (9). S. 4442 - 4453. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

DNAdamage must be repaired in an accurate and timely fashion to preserve genome stability. Cellular mechanisms preventing genome instability are crucial to human health because genome instability is considered a hallmark of cancer. Collectively referred to as the DNA damage response, conserved pathways ensure proper DNA damage recognition and repair. The function of numerous DNA damage response components is fine-tuned by posttranslational modifications, including ubiquitination. This not only involves the enzyme cascade responsible for conjugating ubiquitin to substrates but also requires enzymes that mediate directed removal of ubiquitin. Deubiquitinases remove ubiquitin from substrates to prevent degradation or to mediate signaling functions. The Saccharomyces cerevisiae deubiquitinase Ubp7 has been characterized previously as an endocytic factor. However, here we identify Ubp7 as a novel factor affecting S phase progression after hydroxyurea treatment and demonstrate an evolutionary and genetic interaction of Ubp7 with DNA damage repair pathways of homologous recombination and nucleotide excision repair. We find that deletion of UBP7 sensitizes cells to hydroxyurea and cisplatin and demonstrate that factors that stabilize replication forks are critical under these conditions. Furthermore, ubp7 Delta cells exhibit an S phase progression defect upon checkpoint activation by hydroxyurea treatment. ubp7 Delta mutants are epistatic to factors involved in histone maintenance and modification, and we find that a subset of Ubp7 is chromatin-associated. In summary, our results suggest that Ubp7 contributes to S phase progression by affecting the chromatin state at replication forks, and we propose histone H2B ubiquitination as a potential substrate of Ubp7.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Boehm, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Szakal, Barnabas UNSPECIFIED orcid.org/0000-0001-6888-1383 UNSPECIFIED Herken, Benjamin W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sullivan, Meghan R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mihalevic, Michael J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kabbinavar, Faiz F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Branzei, Dana UNSPECIFIED orcid.org/0000-0002-0544-4888 UNSPECIFIED Clark, Nathan L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernstein, Kara A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-284233
DOI:	10.1074/jbc.M115.671057
Journal or Publication Title:	J. Biol. Chem.
Volume:	291
Number:	9
Page Range:	S. 4442 - 4453
Date:	2016
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEOTIDE EXCISION-REPAIR; EVOLUTIONARY RATE COVARIATION; HISTONE H2B UBIQUITINATION; DNA-REPLICATION STRESS; SACCHAROMYCES-CEREVISIAE; DISTINCT ROLES; PROTEINS; GENES; COMPLEX; DAMAGE Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28423