WHY isse loss hota hai: Replication leading strand pe continuous hoti hai lekin lagging strand pe discontinuous hoti hai (Okazaki fragments, har ek ko RNA primer chahiye). Jab bilkul 3′ end ka last RNA primer remove hota hai, tab polymerase ke paas extend karne ke liye koi upstream 3′-OH nahi hoti us gap ko fill karne ke liye.
Each round of replication⇒lagging-strand end shortens by≈50–200 bp
Buffer: sacrificial DNA taaki shortening junk ko khaye, genes ko nahi.
Cap / protection: ek t-loop + protein complex (shelterin) banata hai taaki cell chromosome ke natural end ko double-strand break na samjhe (jo repair/fusion trigger kar deta).
Bind: Telomerase single-stranded 3′ G-overhang pe dock karta hai; uska RNA template DNA end ke saath base-pair karta hai. (Why? Alignment reading frame set karta hai.)
Elongate: TERT (reverse transcriptase) RNA template read karta hai aur 3′ end pe DNA TTAGGG add karta hai. (Why? G-strand ko bahar ki taraf extend karta hai.)
Translocate: Telomerase aage slide karta hai, apna template re-position karta hai, aur repeat karta hai. (Why? Isse kaafi saare repeats processively add ho paate hain.)
Fill-in: Normal primase + DNA pol + ligase ab extended 3′ overhang ko template ke roop mein use karke C-strand fill karte hain. (Why? Overhang finally polymerase ko extend karne ke liye kuch peeche deta hai.)
WHY DNA polymerase bilkul 3′ end replicate nahi kar sakta? → Terminal gap ke peeche koi primer/template nahi; sirf existing 3′-OH se 5′→3′ extend karta hai.
WHAT do molecular parts telomerase banate hain? → TERT (RT enzyme) + TERC/TR (RNA template).
WHY cancer aksar telomerase reactivate karta hai? → Telomeres maintain karne ke liye → Hayflick limit se bachne ke liye → immortal banne ke liye.
WHAT human telomere repeat sequence hai? → TTAGGG.
What is the end-replication problem?
Linear chromosome 3′ ends poori tarah copy nahi ho sakti kyunki DNA pol ko primer chahiye aur sirf 5′→3′ extend karta hai, terminal RNA primer remove hone pe ek unfillable gap rehta hai.
What is a telomere?
Repetitive non-coding DNA (humans mein TTAGGG) jo chromosome ends cap karta hai; sacrificial buffer ka kaam karta hai aur ends ko breaks samjhe jane se bachata hai.
What is telomerase made of?
Ek reverse transcriptase protein (TERT) aur ek internal RNA template (TERC/TR).
Why does telomerase carry its own RNA template?
Taaki yeh chromosome ki complementary strand ki zaroorat ke bina TTAGGG repeats synthesize kar sake, end-pe-koi-template-nahi ki problem solve karte hue.
Which direction/strand does telomerase extend?
Yeh G-rich strand ke 3′ end (the overhang) ko extend karta hai.
What is the Hayflick limit?
Maximum number (~40–60) of divisions jo ek normal somatic cell telomere shortening se senescence se pehle undergo kar sakti hai.
Why is telomerase usually OFF in somatic cells?
Yeh ek anti-cancer brake ka kaam karta hai — finite divisions uncontrolled proliferation ko rokti hain.
What disease results from a faulty telomerase RNA (TERC)?
Shelterin (aur t-loop structure), end ko DNA-damage repair trigger karne se rokta hai.
Recall Feynman: ek 12-saal ke bacche ko explain karo
Tumhare joote ke laces ke ends pe chhoti plastic tips hoti hain taaki woh fray na hon. Telomeres tumhare DNA ke ends pe wahi tips hain. Har baar jab ek cell khud ko copy karti hai, tip thodi si chhoti ho jaati hai — jaise plastic ghis jaati hai. Agar yeh poori ghis jaaye, toh asli "lace" (tumhare genes) fray ho jaati hai aur cell kaam karna band kar deti hai. Kuch special cells mein telomerase naam ka ek chhota sa tool hota hai jo naya tip wapas chipka deta hai, unhe young rakhta hai. Tumhare zyaadatar cells yeh tool purposely OFF kar dete hain — kyunki ek cell jo forever copy kar sake woh cancer ban sakti hai.
