How yeast cells deal with stalled replication forks
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MINI-REVIEW
How yeast cells deal with stalled replication forks Matan Arbel1 · Batia Liefshitz1 · Martin Kupiec1 Received: 16 April 2020 / Revised: 24 April 2020 / Accepted: 29 April 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract DNA polymerases sometimes stall during DNA replication at sites where DNA is damaged, or upon encounter with proteins or secondary structures of DNA. When that happens, the polymerase clamp PCNA can become modified with a single ubiquitin moiety at lysine 164, opening DNA Damage Tolerance (DDT) mechanisms that either repair or bypass the lesions. An alternative repair mechanism is the salvage recombination (SR) pathway, which copies information from the sister chromatid. SUMOylation of PCNA at the same lysine, or at lysine 127, can recruit the Srs2 helicase, which negatively controls SR. Recently, we have dissected the relationship between SR and the DDT pathways, and showed that overexpression of either the PCNA unloader Elg1, or the Rad52 homologous recombination protein, can bypass the repression by Srs2. Our results shed light on the interactions between different DNA damage repair/bypass proteins, and underscore the importance of PCNA modifications in organizing the complex task of dealing with DNA damage during replication of the genetic material. Keywords Saccharomyces cerevisae · DNA repair · Homologous recombination · Elg1 · PCNA · Genome stability
Introduction During cell growth, the genetic material can be damaged by internal or external sources and cells must deal with this threat to faithfully transmit the genetic material to the next generation. In addition to cellular checkpoint pathways that prevent entry into mitosis with damaged chromosomes, sophisticated DNA repair and DNA damage tolerance mechanisms are in place. These are conserved in all eukaryotes, and much of our knowledge about them comes from the study of simple organisms, such as the yeast Saccharomyces cerevisiae (Adames et al. 2019; Ballew and Lacefield 2019; Gkouskou et al. 2019; Tutaj et al. 2019). The DNA is particularly prone to attack during DNA replication, a time at which the DNA is particularly exposed (Corcoles-Saez et al. 2019; Moriel-Carretero et al. 2019). DNA replication is a complex process, and fork progression may be halted by lesions in the DNA, by secondary structures or by the presence of bound proteins (Owiti et al.
Communicated by Judith Berman. * Martin Kupiec [email protected] 1
School of Molecular Cell Biology and Biotechnology, Tel Aviv University, 69978 Ramat, Aviv, Israel
2019). Cells deal with this situation by either repairing the damage or bypassing it completely, thus preventing the situation from escalating into fatal genomic rearrangements (Singh and Wu 2019). The DNA damage tolerance (DDT) pathway (sometimes also known as the post-replication repair pathway) becomes activated when single-stranded DNA gaps are formed during DNA replication, following DNA polymerase stalling and re-start events (Karras and Jentsch 2010). Central to the
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