SUMO-modified PCNA Recruits Srs2 to Prevent Recombination During S Phase

Nature. 2005 Jul 21;436(7049):428-33. doi: 10.1038/nature03665. Epub 2005 Jun 1.

Abstract

Damaged DNA, if not repaired before replication, can lead to replication fork stalling and genomic instability; however, cells can switch to different damage bypass modes that permit replication across lesions. Two main bypasses are controlled by ubiquitin modification of proliferating cell nuclear antigen (PCNA), a homotrimeric DNA-encircling protein that functions as a polymerase processivity factor and regulator of replication-linked functions. Upon DNA damage, PCNA is modified at the conserved lysine residue 164 by either mono-ubiquitin or a lysine-63-linked multi-ubiquitin chain, which induce error-prone or error-free replication bypasses of the lesions. In S phase, even in the absence of exogenous DNA damage, yeast PCNA can be alternatively modified by the small ubiquitin-related modifier protein SUMO; however the consequences of this remain controversial. Here we show by genetic analysis that SUMO-modified PCNA functionally cooperates with Srs2, a helicase that blocks recombinational repair by disrupting Rad51 nucleoprotein filaments. Moreover, Srs2 displays a preference for interacting directly with the SUMO-modified form of PCNA, owing to a specific binding site in its carboxy-terminal tail. Our finding suggests a model in which SUMO-modified PCNA recruits Srs2 in S phase in order to prevent unwanted recombination events of replicating chromosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Fungal / genetics
  • Chromosomes, Fungal / metabolism
  • DNA Damage
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism*
  • DNA Replication
  • Epistasis, Genetic
  • Mutagenesis / genetics
  • Mutation / genetics
  • Phenotype
  • Proliferating Cell Nuclear Antigen / chemistry
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Protein Binding
  • Recombination, Genetic* / genetics
  • S Phase*
  • SUMO-1 Protein / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Nucleic Acid
  • Substrate Specificity
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism

Substances

  • Proliferating Cell Nuclear Antigen
  • SUMO-1 Protein
  • Saccharomyces cerevisiae Proteins
  • SRS2 protein, S cerevisiae
  • RAD6 protein, S cerevisiae
  • Ubiquitin-Conjugating Enzymes
  • DNA Helicases