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A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress.
Griffin, Wezley C; McKinzey, David R; Klinzing, Kathleen N; Baratam, Rithvik; Eliyapura, Achini; Trakselis, Michael A.
Afiliação
  • Griffin WC; Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
  • McKinzey DR; St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
  • Klinzing KN; Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
  • Baratam R; Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
  • Eliyapura A; Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
  • Trakselis MA; Department of Chemistry and Biochemistry, Baylor University, Waco, TX, 76706, USA.
Nat Commun ; 13(1): 5090, 2022 08 30.
Article em En | MEDLINE | ID: mdl-36042199
The minichromosome maintenance (MCM) 8/9 helicase is a AAA+ complex involved in DNA replication-associated repair. Despite high sequence homology to the MCM2-7 helicase, a precise cellular role for MCM8/9 has remained elusive. We have interrogated the DNA synthesis ability and replication fork stability in cells lacking MCM8 or 9 and find that there is a functional partitioning of MCM8/9 activity between promoting replication fork progression and protecting persistently stalled forks. The helicase function of MCM8/9 aids in normal replication fork progression, but upon persistent stalling, MCM8/9 directs additional downstream stabilizers, including BRCA1 and Rad51, to protect forks from excessive degradation. Loss of MCM8 or 9 slows the overall replication rate and allows for excessive nascent strand degradation, detectable by increased markers of genomic damage. This evidence defines multifunctional roles for MCM8/9 in promoting normal replication fork progression and genome integrity following stress.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reparo do DNA / Replicação do DNA Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reparo do DNA / Replicação do DNA Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido