The Aspergillus nidulans musN gene encodes a RecQ helicase that interacts with the PI-3K-related kinase UVSB

A F Hofmann1, S D Harris

  • 1Department of Microbiology, University of Connecticut Health Center, Farmington, Connecticut 06030-3205, USA.

Genetics
|January 10, 2002
PubMed

Insights

The study identifies MUSN, a RecQ helicase in Aspergillus nidulans, as crucial for DNA damage response and recovery. Its interaction with UVSB and homologous recombination pathways sheds light on DNA repair mechanisms.

Area of Science:

  • Molecular biology
  • Genetics
  • DNA repair mechanisms

Background:

  • The UVSB protein, a PI-3K-related kinase, is essential for DNA damage response in Aspergillus nidulans.
  • The musN227 mutation partially suppresses defects caused by uvsB mutations, indicating a functional link.

Purpose of the Study:

  • To elucidate the mechanism by which the musN227 mutation suppresses uvsB defects by cloning and characterizing the musN gene.
  • To understand the role of MUSN in DNA damage response and its relationship with other DNA repair pathways.

Main Methods:

  • Gene cloning and sequencing of the musN gene.
  • Phenotypic characterization of musN mutant alleles, including growth assays and genotoxin sensitivity tests.
  • Analysis of genetic interactions between musN, uvsB, and uvsC mutations.

Main Results:

  • The musN gene encodes a RecQ helicase homologous to S. pombe Rqh1, S. cerevisiae Sgs1, and human BLM and WRN.
  • MUSN plays a role in responding to various genotoxic agents.
  • The slow growth and genotoxin sensitivity of musN null mutants are partially suppressed by the uvsC114 mutation, which affects homologous recombination.
  • Evidence suggests MUSN promotes recovery from DNA damage.
  • A specific musN mutation (musN227) may block recovery, and this, along with recombination intermediates, suppresses uvsB defects.
  • Another RecQ helicase, ORQA, has overlapping functions with MUSN.

Conclusions:

  • MUSN is a novel RecQ helicase involved in DNA damage response and recovery in Aspergillus nidulans.
  • The interaction between MUSN, UVSB, and homologous recombination pathways is critical for maintaining genomic stability.
  • Understanding MUSN's function provides insights into conserved DNA repair mechanisms across eukaryotes.

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...