The Rad5 helicase activity is dispensable for error-free DNA post-replication repair

Ball, Lindsay G.; Xu, Xin; Blackwell, Susan; Hanna, Michelle; Lambrecht, Amanda D.; Xiao, Wei

doi:10.1016/j.dnarep.2014.02.016

Cited by 28 publications

(46 citation statements)

References 45 publications

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“…For example, fork regression mediated by Rad5 could occur prior to and facilitate strand invasion as part of template switching [53]. Surprisingly, when physically fused to Ubc13 or Mms2, the ATPase/helicase mutated Rad5 behaves indistinguishably from that of wild-type Rad5, causing the authors to conclude that the Rad5 fork regression activity is dispensable for error-free DDT [56]. The above observations lend support to the template switching model and involvement of HR in error-free DDT.…”

Section: The Relationship Between Fork Regression and Template Switchsupporting

confidence: 60%

“…As expected, it was found that the Rad5 ATPase/helicase mutation only affects error-free DDT. Unexpectedly, this mutation also abolishes the physical interaction of Rad5 with Ubc13 [56], making it questionable whether the Rad5 fork regression activity contributes to error-free DDT in vivo. It should be noted that the two proposed models for the mechanism of error-free DDT do not have to be mutually exclusive.…”

Section: The Relationship Between Fork Regression and Template Switchmentioning

confidence: 96%

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Error-free DNA-damage tolerance in Saccharomyces cerevisiae

Blackwell

Lin

et al. 2015

Mutation Research/Reviews in Mutation Research

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Section: The Relationship Between Fork Regression and Template Switchsupporting

confidence: 60%

Section: The Relationship Between Fork Regression and Template Switchmentioning

confidence: 96%

Error-free DNA-damage tolerance in Saccharomyces cerevisiae

Blackwell

Lin

et al. 2015

Mutation Research/Reviews in Mutation Research

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“…Both dependent and independent relationships between the two domains of Rad5 have been proposed. Mutations of individual Rad5 helicase motifs show either epistatic or additive genetic relationships with mutations affecting PCNA poly-ubiquitination (9,11,24,25). These results imply very different models for how Rad5 functions in damage tolerance.…”

Section: Introductionmentioning

confidence: 99%

Concerted and differential actions of two enzymatic domains underlie Rad5 contributions to DNA damage tolerance

Choi

Batke

Szakál

et al. 2015

Nucleic Acids Research

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Many genome maintenance factors have multiple enzymatic activities. In most cases, how their distinct activities functionally relate with each other is unclear. Here we examined the conserved budding yeast Rad5 protein that has both ubiquitin ligase and DNA helicase activities. The Rad5 ubiquitin ligase activity mediates PCNA poly-ubiquitination and subsequently recombination-based DNA lesion tolerance. Interestingly, the ligase domain is embedded in a larger helicase domain comprising seven consensus motifs. How features of the helicase domain influence ligase function is controversial. To clarify this issue, we use genetic, 2D gel and biochemical analyses and show that a Rad5 helicase motif important for ATP binding is also required for PCNA poly-ubiquitination and recombination-based lesion tolerance. We determine that this requirement is due to a previously unrecognized contribution of the motif to the PCNA and ubiquitination enzyme interaction, and not due to its canonical role in supporting helicase activity. We further show that Rad5′s helicase-mediated contribution to replication stress survival is separable from recombination. These findings delineate how two Rad5 enzymatic domains concertedly influence PCNA modification, and unveil their discrete contributions to stress tolerance.

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“…Indeed, PCNA polyubiquitlylation-dependent template switching in yeast is dependent on the key HR protein Rad51, demonstrating a functional overlap between template switching and HR (Branzei et al, 2008;Minca and Kowalski, 2010). An alternative mechanism for template switching through the reversal and regression of stalled replication forks (Atkinson and McGlynn, 2009;Higgins et al, 1976) is supported by the structure-specific helicase ability of Rad5 (Blastyak et al, 2007), though recently the helicase activity of Rad5 was shown to be dispensable for template switching (Ball et al, 2014).…”

Section: Introductionmentioning

confidence: 99%