TABLE 1.

Functions of proteins involved in the regulation of telomere length homeostasis in Saccharomyces cerevisiae.

Proteins		Functions
Telomere capping complexes:
Cdc13-Stn1-Ten1	CST complex	Protects telomere end from degradation (Grandin et al., 2001) Restricts telomerase access to telomere at the end of S phase (Churikov et al., 2013).
Ku70-Ku80	Yku complex	Protects telomere end from telomere-end resection (Vodenicharov et al., 2010; Shi et al., 2013).
Rap1-Rif1-Rif2		Restricts telomerase access to telomere to inhibit telomere extension of overlengthened telomere (Wotton and Shore, 1997; Goudsouzian et al., 2006; Hirano et al., 2009). Inhibits exonucleolytic degradation of telomere by preventing the association of Mre11-Rad50-Xrs2 (MRX) complex with telomere (Bonetti et al., 2010).
Telomere capping proteins:
Npl3, Cdc2	hnRNP-related proteins	Prevents telomere end from being recognized as DNA break (Lee-Soety et al., 2012)
Rad6–Bre1–H2Bub1		Promotes telomere extension by inducing telomere-end resection (Wu et al., 2017)
Mre11-Rad50-Xrs2	MRX complex	Executes 5′ to 3′ exonuclease activity to synthesize 3′ overhang for Cdc13 binding at telomere (Diede and Gottschling, 2001) Mediates telomerase tethering to telomere (Tsukamoto et al., 2001). Protects uncapped telomere from exonucleolytic degradation during telomere extension (Vodenicharov and Wellinger, 2007; Wu et al., 2018).
Cdc13	ssDNA-binding protein	Protects telomere end (Nugent et al., 1996; Pennock et al., 2001). Promotes telomerase tethering to telomere (Nugent et al., 1996; Chandra et al., 2001)
Mec1	Phosphoinositide 3-kinase-related kinases (PIKKs)	Phosphorylates Cdc13 to mediate telomerase tethering to telomere (Tseng et al., 2006; Yang et al., 2017). Phosphorylates Rap1 to strengthen the interaction of Rap1 with Rif1 for promoting telomere end protection (Yang et al., 2017).
Tel1	Phosphoinositide 3-kinase-related kinases (PIKKs)	Recruited by MRX complex to short telomere (Nakada et al., 2003, 1; McGee et al., 2010) to promote telomerase tethering to telomere (Goudsouzian et al., 2006; Sabourin et al., 2007). Phosphorylates Cdc13 to mediate telomerase tethering to telomere (Tseng et al., 2006; Yang et al., 2017). Phosphorylates Rap1 to strengthen the interaction of Rap1 with Rif1 to promote telomere end protection (Yang et al., 2017).
Mre11	Double-strand break repair protein	Promotes telomerase tethering to telomere (Goudsouzian et al., 2006).
RPA	ssDNA-binding protein (replication protein A)	Promotes telomerase activity during telomere extension (Schramke et al., 2004; Luciano et al., 2012).
Cdk1	Cyclin-dependent kinase	Regulates telomere extension (Frank et al., 2006).
Pif1	Helicase	Unwinds G-quadruplex at telomere end to enable telomerase-mediated telomere extension and avoid DNA break (Paeschke et al., 2011)
Sgs1	Helicase	Unwinds G-quadruplex at telomere end to enable telomerase-mediated telomere extension (Huber et al., 2002). Generates type II telomerase-deficient survivors (Huang et al., 2001).
Elo3	Fatty acid elongase	Synthesizes very long-chain fatty acids (VLCFAs) (Kvam et al., 2005) to maintain telomere length through mediation of Yku (Ponnusamy et al., 2008).
Kcs1	Inositol hexakisphosphate and inositol heptakisphosphate kinase	Synthesizes inositol phosphates, which negatively affect telomere-maintaining role of Elo3 through mediation of Yku (Ponnusamy et al., 2008).
Ipk2	Inositol polyphosphate multikinase
Sit4	Protein serine/threonine phosphatase	Synthesizes protein phosphatase 2A (PP2A) which dephosphorylates Sir3 to maintain the heterochromatin structure for telomere stabilization (Chan and Blackburn, 2002; Hayashi et al., 2005).
Def1	RNA polymerase II degradation factor	Positive regulator in telomere maintenance and required for the generation of type II telomerase-deficient survivors (Chen et al., 2005).
Tsa1	Thioredoxin peroxidase	Major reactive oxygen species (ROS) scavenger (Iraqui et al., 2009) that prevents telomere overextension due to ROS (Lu et al., 2013).
Rnr1	Major subunit of ribonucleotide reductase (RNR)	Provides precursors for synthesis of deoxynucleoside triphosphates (dNTPs) required for telomerase-mediated telomere extension (Maicher et al., 2017).
ESCRT-0, –I,–II, and –III	Endosomal sorting complex required for transport (ESCRT)	Maintains telomere length by participating in telomerase-dependent telomere extension (Dieckmann et al., 2016).
Pol ϵ and Pol δ	DNA polymerase	Maintain telomere length (Ohya et al., 2002) by synthesizing chromosomal DNA strands (McElhinny et al., 2008) Exhibits 3′-5′ exonuclease activity for telomeric ssDNA repair during cell cycle arrest (Ohya et al., 2002; Henninger and Pursell, 2014).
Pol α-primase complex		Synthesizes RNA-DNA primer required for synthesis of chromosomal DNA strands (Churikov et al., 2013; Pfeiffer and Lingner, 2013).
Yra1	RNA-binding protein required for mRNA export from nucleus	Overexpression causes telomere shortening (Gavaldá et al., 2016).