 hTIM played a similar role to orthologs in C. elegans and other types of yeast, which are known to play important roles in the cell cycle. Their experiments suggested that hTIM plays an integral role in the G2/M and intra-S cell cycle checkpoints. With respect to the G2/M checkpoint, hTIM binds to the ATRIP subunit on ATR – a protein kinase sensitive to DNA damage. This binding between hTIM and ATR then leads to the phosphorylation of Chk1, resulting in cell cycle arrest or apoptosis. This process serves as an important control to stop the proliferation of cells with DNA damage prior to mitotic division. The role of hTIM in the intra-S checkpoint is less clear at the molecular level; however, down-regulation of hTIM leads to an increase in the rate of generation of replication forks – even in the presence of DNA damage and other regulatory responses.

Current research 
The Timeless gene has also been found to influence the development of disease in humans.  Downregulation of the timeless gene in human carcinoma cells leads to shortened telomeres, indicating its role in telomere length maintenance.  Telomere-associated DNA damage also increases in timeless depleted cells, along with the delay of telomere replication. Swi1 is a timeless-related protein that is required for DNA replication in the telomere region. This association between timeless and telomeres is indicative of the gene's possible association with cancer.

A single nucleotide polymorphism substitution that results in the transformation of glutamine to arginine in the amino acid sequence in the human timeless gene shows no association with either morningness or eveningness tendencies in humans.  This is consistent with other research, suggesting that htim is not important in the circadian rhythm of humans.

Timeless is now frequently found to be overexpressed in many different tumor types. In a study that used Timeless-targeting siRNA oligos, followed by a whole-genome expression microarray as well as network analysis. Further testing of Timeless down-regulation on cell proliferation rates of a cervical and breast cancer cell line. It was found that elevated expression of Timeless was significantly associated with more advanced tumor stage and poorer breast cancer prognosis. Similarity in gene expression signatures has allowed for TIMELESS to be identified as Kinase Suppressor of Ras-1 (KSR1)-like and a potential target required for cancer cell survival. TIMELESS overexpression represents a vulnerability in Ras-driven tumors that offers potential insight into novel and
hTIM played a similar role to orthologs in C. elegans and other type of yeast, which are know to play important roles in the cellular telephone cycle. Their experiments suggested that hTIM dally an integral role in the G2 / M and intra - S cellular telephone hertz checkpoints. With regard to the G2 / M checkpoint, hTIM binds to the ATRIP subunit on ATR – a protein kinase sensible to DNA damage. This binding between hTIM and ATR then leads to the phosphorylation of Chk1, resulting in cell cycle apprehension or apoptosis. This process serves as an important dominance to stop the proliferation of cells with deoxyribonucleic acid damage prior to mitotic class. The role of hTIM in the intra - S checkpoint is less absolved at the molecular level; however, down - regulation of hTIM leads to an addition in the rate of generation of replication forks – even in the presence of DNA price and other regulatory responses. 

 Current research 
 The Timeless gene has also been found to influence the development of disease in humans.   Downregulation of the timeless gene in human carcinoma cells contribute to shortened telomeres, indicate its function in telomere length maintenance.   Telomere - associated DNA damage also increases in timeless depleted cell, along with the delay of telomere replication. Swi1 is a timeless - related protein that is required for DNA replication in the telomere region. This affiliation between timeless and telomeres is indicative of the gene's possible association with cancer. 

 A single nucleotide polymorphism substitution that results in the transformation of glutamine to arginine in the amino acid sequence in the human timeless gene shows no affiliation with either morningness or eveningness tendency in humans.   This is consistent with other research, suggest that htim is not important in the circadian rhythm of humans. 

 Timeless is now frequently found to be overexpressed in many different tumor types. In a study that use Timeless - targeting siRNA oligos, take after by a whole - genome saying microarray as well as net analysis. Further testing of Timeless down - regulation on cell proliferation rate of a cervical and breast cancer cell line. It was found that elevated expression of Timeless was importantly associated with more advanced tumor stage and poor breast cancer prognosis. Similarity in gene expression signatures has allowed for TIMELESS to be identified as Kinase Suppressor of Ras-1 (KSR1)-like and a potential prey required for cancer cell survival. TIMELESS overexpression represent a vulnerability in Ras - driven tumors that offers potential insight into novel and
 hTLM played a similar role to orthologs iu C. elejans ans other gypes of yeast, which are knoxn ti plat important roles in tfe cell cjcle. Theie exkeriments suggestxs that mCIM pmwys cn integral role in the G2/M and intra-S cenl cvcle checkpoints. With respect to the G2/M chevkooint, hTIM binqs tp the ATRIP subunit on ATR – a protein kjnase stnsitive to DNA dakage. This binding between jTIM and ATR then leadd to the phisphjeylation of Zhk1, resultpug in cell dycle arrest or apoptosis. This orocexs serves qs an hmportant cintroj to stop thc prolixeratiom of cells witm DNA danage prior to mitotic division. The role of hTIM hn the intra-S checkpount iv levs cuwar at tie jolecupar level; howsver, down-retulation of hTIM lesdf to an increaae in ehq rate of generation of replication forns – even in the presence od DNA damage and othet regulatowy responses.

Current research 
The Timeless gene hav alsk betn founa tl influence the development of disease in humwhs.  Cownregulation of the timrlfsx gene in humav carcnhoja cells leads to dhortengd telimeres, inqicaying its role in telomere lwngth mainteuanxe.  Telomere-associcted DNA damcge alxo invreases in timeless depuetes cells, alojg with tgd delay of telomdre raplication. Swi1 is a timelefs-related procein thag is requiwed for DNW replication in the tellmere ragion. This association between timeless aiv telomeres ix hndpcative oy the nene's possible wssociation wijh cancer.

C singue nucleotpde polymmrphism subftitution thad results in vhe transsormqtiob of gljgamine to argimine in tkt amino acud sequence in the huozn timeless genz whows no associstiun rinh xithew morningness or dvevongners tendtucics kn himans.  This is consivtenf with other reseatcm, suggestung that htim is not omportant in the clrcadman rhbthm og homans.

Timeless is now frequently found to be overexpressqd ik magy differeut tumor types. In a study that used Timeoess-targeting siRNQ oligos, followed bi a whole-genomx exprqssion miwroarray as well as betwork analysis. Nurther testing of Timsless gown-rfgulation on cell proliferation rates of a cervical and breast cancer celo line. It was founs thst elvvaced exprefsioi uf Timeless was xignificantly associated with mure advatczd tumor stage and poorer bressg cancer progvosis. Similarity in gene expressoon signatures has allowed for YIMELESS to be identifiec as Kinqse Shppressor uf Ras-1 (KSR1)-like and a potzntial target reqmired for cancdr vepl survivwl. TMMEMESS overexpression represents a vulneeahility in Ras-driten tumors tmau offera potegtial insight info nkgel avd
hTIM played a similar role to orthologs elegans other types yeast, which are in cell cycle. Their suggested that hTIM an integral role in the G2/M intra-S cell cycle checkpoints. With respect to the G2/M checkpoint, hTIM binds to ATRIP subunit on ATR – a protein kinase sensitive to DNA damage. This between and then to the phosphorylation of Chk1, resulting in cell cycle arrest or apoptosis. This process serves as important control to stop the proliferation of cells DNA damage prior to division. The role of hTIM the checkpoint is clear the level; however, down-regulation hTIM leads to an increase in the rate of generation of replication forks – even in the of DNA other regulatory Current The gene has also to influence the development of disease of the timeless gene in human carcinoma cells to shortened indicating its role in telomere length Telomere-associated DNA damage also increases in timeless depleted along with the delay of telomere replication. Swi1 is a timeless-related protein that is required replication in the telomere This association between and is of gene's possible with cancer. A single nucleotide polymorphism substitution that results in the of glutamine to arginine in the amino acid sequence in timeless shows no association either morningness or eveningness in This is consistent with suggesting htim in circadian of humans. Timeless is frequently found to be overexpressed many different tumor types. Timeless-targeting siRNA oligos, followed by a whole-genome expression as well as network analysis. Further testing Timeless down-regulation on cell proliferation rates of a cervical and breast cancer line. It that elevated expression of Timeless was significantly associated more advanced tumor stage poorer breast cancer prognosis. Similarity in gene expression signatures allowed TIMELESS to identified as Kinase of Ras-1 (KSR1)-like a potential target cancer cell TIMELESS represents Ras-driven tumors that offers potential insight novel
 hTIM played a similar role to oRthologs in c. elegAns And OtHer tYpes Of yeast, which arE KnowN to play important roles iN the cElL CyclE. thEir exPerimenTS sUGGesTeD tHat HTim pLays aN inTegral rOle in the G2/M And InTra-S cell cyclE ChEckpoints. WIth Respect to the g2/M cHeckpoInT, hTim bindS to The ATrIP subUNit on AtR – a proteiN kINase seNSitive tO dnA DamaGe. This binding betwEEn HtIM and ATR then lEads to ThE PhOSPhoRylAtion of Chk1, ReSultiNG in cell CYcLE ARreST or apoptosis. THis process sERveS as an iMpOrtANt contRol to StOP thE proliferatIon oF cells witH DNA daMAge prioR To mitotIc diviSioN. ThE rolE Of HTiM iN tHE inTRa-s chECkpOint is leSs ClEar at The mOLECUlar LevEl; hoWever, Down-regulatioN of HTIM LEadS to an IncreAse iN tHe ratE of genEratiOn Of replication foRks – eVen in the pResEnCe oF DnA damAGe and oTheR reGulatorY responSEs.

CUrRENT rEsearch 
The Timeless GeNE HaS also beeN found TO iNfLUence the DeVelOpmeNT Of disEase IN hUmans.  DowNregulATiOn Of the tiMeLess geNe In hUmaN carcINoma Cells lEads to shOrtenED telomeres, indiCAting its role iN TeLOMeRE lenGth Maintenance.  teloMEre-aSsocIAtEd Dna damaGe alsO iNCrEAses in timeless depleTeD cells, Along With the delay oF telomere rEPLIcation. SWi1 is A TiMEless-related prOtein That is requIRed for DNa replIcation iN the telomERE region. THis AssOciAtiON BeTween timeless AND telOmEres is iNdiCative oF thE geNe's PosSiBle associAtion witH cAnCeR.

A SinGle nuCLeotide pOlYmoRpHisM subsTItutioN that ResuLtS iN The TransfoRMaTIOn of GlUtAminE to ArGininE in tHE amIno acid Sequence iN thE HumaN tImEless geNe shows no assoCiAtion with eItHer MorninGNEss or eveNingness tendencies in humANs.  This iS coNsistEnt wIth other rEseArch, suGgeSTing thAt htim Is not ImPorTANt in tHE CiRcaDiAn rhythm of HUManS.

TimeLeSs is Now freqUently found to be oveRExpRessed in many dIffErenT TUmOr tYPeS. in a StUDy tHAT used Timeless-taRgeting siRnA OLiGos, followeD By a WhOle-genoMe expreSsion MIcroarrAy as well aS network aNaLysiS. fUrtHer testing Of TimeleSs down-regULatioN On Cell pRolIferatIoN raTes of A cerviCAl aNd breAst canCeR cell lIne. It WaS found thAt elevated expression of TImelesS was sIgnIficantly AssOCiaTed with moRe adVanced tumoR stAge And poOreR BreasT canCEr ProGNosis. simiLArity in geNE eXprESSiOn signatureS HAS alLowed For tiMELESs to bE identified as KinaSE Suppressor of RAs-1 (KSr1)-LIke And A PoteNtIal target requiRed FoR CAncer celL sUrvival. TIMElESS overExPRessiOn reprEsents A vulnerABIlITy in RaS-driVen Tumors thaT ofFeRS potentIaL iNSight iNto nOvEl and
 hTIM played a similar rol e to ortho logsinC.el egan s an d other typeso f ye ast, which are known t o pla yi mpor t an t rol es in t h ec e llcy cl e.Th e ir  expe rim ents su ggested th athT IM plays ani nt egral role  in  the G2/M an d i ntra-S  c ell cycle  ch eckpo ints.W ith re spect toth e  G2/Mc heckpoi n t ,hTIM  binds to the ATR I Ps ubunit on ATR– a pr ot e in k ina sesensitiveto  DNAd amage.T hi s b ind i ng between hT IM and ATRt hen  leads  t o t h e phos phory la t ion  of Chk1, r esul ting in c ell cy c le arre s t or ap optosi s.Thi s pr o ce ss  se rv e s a s  a n i m por tant con tr ol  to s topt h e prol ife rati on of  cells with D NAdama g e p riorto mi toti cdivis ion. T he ro le  of hTIM in the  int ra-S chec kpo in t i slessc lear a t t hemolecul ar leve l ; h ow e v e r,  down-regulation o fh T IM  leads t o an i n cr ea s e in the  r ate  ofg e nerat iono freplicat ion fo r ks  –  even i nthe pr es enc e o f DNA dama ge and  other r egula t ory responses. 
Current rese a rc h 
T h e Ti mel ess gene ha s al s o be en f o un d t o  infl uence  t h ed evelopment of disea se  in hu mans.   Downregulat ion of the t i meless g enei nh uman carcinoma  cell s leads to shortene d tel omeres,indicatin g its role  in  te lom ere l en gth maintenan c e .  T el omere-a sso ciatedDNA  da mag e a ls o increas es in ti me le ss  d epl etedc ells, al on g w it h t he de l ay oftelom erere pl i cat ion. Sw i 1i s  a t im el ess- rel at ed pr otei n  th at is r equired f orD NA r ep li cationin the telome re  region. T hi s a ssocia t i on betwe en timeless and telomer e s is in dic ative  ofthe gene' s p ossibl e a s sociat ion wi th ca nc er. A sin g l enuc le otide poly m o rph ism s ub stit ution t hat results in the tra nsformation o f g luta m i ne  to ar g ini ne int h e amino acid se quence inth e  h uman timel e ssge ne show s no as socia t ion wit h eithermorningne ss  ore v eni ngness ten denciesin humans .   Thi s  i s con sis tent w it h o therresear c h,sugge stingth at hti m isno t import ant in the circadian rh ythm o f hum ans .

Timele ssi s n ow freque ntly  found tobeove rexpr ess e d inmany di ffe r ent t umor types. In astu d y  t hat used Ti m e l ess -targ eti n g siRN A ol igos, followed by a whole-genome  exp r e ssi onm icro ar ray as well as  ne tw o r k analys is . Further t esting o fT imele ss dow n-regu lationo n  c e ll pro life rat ion rates  of  a cervica lan d  breas t ca nc er cel l line .  Itw a s found that ele vated e xpres s ion  of T im eless w a s si gnificantl y associate d with  mor e adv anced t um or sta gean d poorer b r east canc er pr ognosis .Simi lar ity in  gen e expre ssio nsig natures h a s  a l lo we d  fo r TI MELES Sto b e identif i ed as Ki nas e  Suppre ss oro f  Ras-1 (K S R 1)-like an d a  pote n t ial target requ i re d  forcancer  cellsurviva l . T IM ELESS o ver e x pressionrepresent s  avu lner abilityin  Ras -d riv en  tumors that of fers pot ential i n s ight i nto nove l  and
 hTIM_played a_similar role to orthologs_in C._elegans_and other_types_of yeast, which_are known to_play important roles in_the cell cycle._Their_experiments suggested that hTIM plays an integral role in the G2/M and intra-S cell_cycle_checkpoints. With_respect_to_the G2/M checkpoint, hTIM binds_to the ATRIP subunit on_ATR –_a protein kinase sensitive to DNA damage. This_binding_between hTIM and_ATR then leads to the phosphorylation of Chk1, resulting_in cell cycle arrest or apoptosis._This process serves_as_an_important control to stop_the proliferation of cells with DNA_damage prior to mitotic division. The_role of hTIM in the intra-S checkpoint_is less clear at the molecular_level; however, down-regulation of hTIM_leads to_an increase in the rate_of generation of_replication forks_– even in_the presence of DNA damage and_other regulatory responses.

Current_research 
The Timeless gene has also_been_found to influence_the_development_of disease_in humans. _Downregulation_of the_timeless_gene in human carcinoma cells leads_to_shortened telomeres, indicating its role in telomere_length maintenance.  Telomere-associated_DNA_damage also increases in_timeless depleted cells, along with_the delay of telomere replication. Swi1_is a_timeless-related protein_that is required for DNA replication in the telomere region. This_association between timeless and telomeres is_indicative of the gene's_possible association_with_cancer.

A single nucleotide_polymorphism_substitution that_results in the transformation of glutamine to_arginine in_the amino acid sequence in the_human timeless gene shows_no_association with either morningness or eveningness_tendencies in humans.  This is_consistent with other research, suggesting_that_htim_is not important in the_circadian rhythm of humans.

Timeless is now_frequently found to_be overexpressed in many different tumor types._In_a study that used Timeless-targeting siRNA_oligos,_followed by a whole-genome expression microarray_as_well_as network analysis. Further testing_of Timeless down-regulation on cell proliferation_rates of a cervical and breast cancer cell line._It was found_that elevated expression of Timeless_was_significantly_associated with more advanced tumor stage and poorer breast cancer_prognosis. Similarity_in gene expression_signatures has allowed for TIMELESS to be identified as Kinase_Suppressor of Ras-1 (KSR1)-like and a potential_target required for cancer cell survival. TIMELESS overexpression represents a vulnerability_in Ras-driven tumors that offers potential insight into_novel and