The role of DNA helicases in promoting progression of DNA replication through sites that are difficult to replicate is of particular importance for our understanding of maintenance of genomic stability. During each cell cycle, DNA replication needs to overcome multiple obstacles, such as DNA-bound proteins, DNA secondary structures, and damaged DNA. The goal of our research is to understand how the Pif1-family of helicases, conserved from yeast to metazoans, aid DNA replication across barriers in general, but particularly at telomeres, which are known to impede replication and whose integrity is fundamental to genome stability.
Sparks MA, Burgers PM, Galletto, R.
Pif1, RPA and FEN1 modulate the ability of DNA polymerase δ to overcome protein barriers during DNA synthesis
J. Biol. Chem. (2020) 295(47):15883-15891 doi: 10.1074/jbc.RA120.015699 PMID: 32913126
Singh SP, Soranno A, Sparks MA, Galletto R.
Branched unwinding mechanism of the Pif1 family of DNA helicases.
Proc Natl Acad Sci USA 2019 Dec 3. doi: 10.1073/pnas.1915654116. PubMed PMID: 31744872.
Sparks MA, Singh SP, Burgers PM, Galletto R.
Complementary roles of Pif1 helicase and single stranded DNA binding proteins in stimulating DNA replication through G-quadruplexes.
Nucleic Acids Res. 2019 Jul 24. pii: gkz608. doi:10.1093/nar/gkz608. PubMed PMID: 31340040.
Singh SP, Kukshal V, Galletto R.
A stable tetramer is not the only oligomeric state that mitochondrial single-stranded DNA binding proteins can adopt.
J Biol Chem. 2019 Mar 15;294(11):4137-4144. doi: 10.1074/jbc.RA118.007048. Epub 2019 Jan 7. PubMed PMID: 30617184; PubMed Central PMCID: PMC6422086.
Mondol T, Stodola JL, Galletto R, Burgers PM.
PCNA accelerates the nucleotide incorporation rate by DNA polymerase δ.
Nucleic Acids Res. 2019 Feb 28;47(4):1977-1986. doi: 10.1093/nar/gky1321. PubMed PMID: 30605530; PubMed Central PMCID: PMC6393303.
Dahan D, Tsirkas I, Dovrat D, Sparks MA, Singh SP, Galletto R, Aharoni A.
Pif1 is essential for efficient replisome progression through lagging strand G-quadruplex DNA secondary structures.
Nucleic Acids Res. 2018 Dec 14;46(22):11847-11857. doi: 10.1093/nar/gky1065. PubMed PMID: 30395308; PubMed Central PMCID: PMC6294490.
Geronimo CL, Singh SP, Galletto R, Zakian VA.
The signature motif of the Saccharomyces cerevisiae Pif1 DNA helicase is essential in vivo for mitochondrial and nuclear functions and in vitro for ATPase activity.
Nucleic Acids Res. 2018 Sep 19;46(16):8357-8370. doi: 10.1093/nar/gky655. PubMed PMID: 30239884; PubMed Central PMCID: PMC6144861.
Singh SP, Kukshal V, De Bona P, Antony E, Galletto R.
The mitochondrial single-stranded DNA binding protein from S. cerevisiae, Rim1, does not form stable homo-tetramers and binds DNA as a dimer of dimers.
Nucleic Acids Res. 2018 Aug 21;46(14):7193-7205. doi: 10.1093/nar/gky530. PubMed PMID: 29931186; PubMed Central PMCID: PMC6101547.