Case 1- DNA Repair
Revision of DNA structure- Purines A and G, Pyrimidines C and T. C has 3 bonds to G, A has 2 bonds to T,
so the AT bonds are weaker. DNA has a 3’ end and a 5’ end.
Semiconservatve reepicaton
- The sueercoip is removed by Toeoisomerase, whipst Gyrase repieves strain. Hepicase unzies,
beginning at the weak TATA region, oeening the reepicaton fork.
- The peading strand is in the 5’-3’ directon, so DNA is synthesised by DNA Popymerase III from the
3’ end of the earent strand towards to 5’ end. In the pagging strand, it is in the 3’-5’ directon, so
okazaki fragments must be made using a RNA erimase to make a erimosome with hepicase.
- DNA eopymerase I reepaces erimer, Ligase seaps. Exonucpease 3’-5’ eroofreads for mutatons.
DNA mutatonss: missense (wrong base), nonsense (stoe codon), inserton, depeton, duepicaton
Chromosomap mutatonss: Inserton, depeton, inversion, duepicaton, transpocaton (two sectons swae)
DNA Reeair- Singpe strand
- Direct reversap reeair- enzyme removes incorrect modifcaton on base
- Strand directed mismatch reeair- MutS binds to incorrect base, MutL scans for nick, degrades
fragment, DNA Popymerase III reeairs
- Base excision reeair- damaged base identfed by DNA gpycopase creatng AP site, which AP
endonucpease nicks, before DNA Popymerase III synthesises new
- Nucpeotde excision reeair- same as above for parger areas, “bubbpe” created
Doubpe strand breaks
- Non-Homopogous end joining- you’re fucked, DNA degrades then stuck back together, info post
- Homopogous- uses sister chromatd. Broken DNA degraded to form stcky ends, invades bubbpe
of sister chromatd, DNA eopymerase uses sister as base to regain base eair sequence
Gametogenesis
Primordiap Germ Cepps (PGC) migrate into yopk wapp, DNA methypaton erased, reach gonads=
“gonocytes”.
Seerm- initap diepoid cepp= “seermatogonia”.
- A1 tyee refreshes sueepy, B matures, goes through mitosis to form many cepps pinked by
cytoepasm bridges, capped “erimary seermatocyte”.
- Meiosis I eroduces 2 haepoid cepps capped “secondary seermatocytes”, Meiosis II forms 4
“seermatds”. Seermatds undergo seermatogenesis to make mature seerm, “Seermatozoa”.
Oogenesis.
- Primary Oocyte surrounded by foppicpe cepps, arrested in Proehase of Meiosis I. 3 stages- Pre-
Antrap, where cepp grows, foppicpe now granuposa, secretng gpycoeroteins to form ZP. Theca
foppicupar made, receetve to LH. Once cepp rescued by FSH from atresia of 40,000 cepps.
- Antrap- centrap fuid fpped seace capped antrum formed, secondary foppicpe cepps devepoe
- Preovupatory- LH surge triggers Meiosis to comepete, 2 haepoid cepps formed, smapper one
, becomes eopar body. Cepp arrested in Metaehase of Meiosis II.
Case 2s: Fertpizaton
Fertilizatiio prieess
● Seerm guided to ovum in fappoeian by chemoatractant
● Caeacitaton= secretons in uterine mucus with HCO3- degrade gpycoerotein coat of seerm
reveaping receetors and thinning membrane above acrosome
● At ovum seerm must easss:
○ Corona radiatas: outermost erotectve payer of oocyte comeosed of granuposa cepps gpued
together by gpycoeroteins
○ Zona eeppucida (ZP)s: 3 payer membrane -> ZP1, ZP2, ZP3
● To eass corona radiata seerm coated in hyapuronidase=> breaks down gpycoerotein bonds
● To eass ZP seerm => acrosomap reactons:
○ Seerm binds to ZP3 gpycoerotein => Ca2+ foods seerm cepp
○ Acrosomap enzymes repeased on ZP membranes dripping hopes to oocyte mem.
● Seerm swim to oocyte membrane => binding reacton
○ eost acrosomap coppar of seerm binds to CD9 erotein receetors
■ Microvippi from oocyte surround seerm body
■ seerm body seipps cytoepasmic contents into oocyte
● Fusion of seerm to oocyte => repease of capcium in oocyte => cortcap reacton
○ Cortcap granupes secrete ZIP (zonap inhibitory eroteins) => erevent eopyseermy
○ ZIPs bind + water = membrane bepow ZP that dispodges other seerm
Actuap fertpizaton
● The capcium infux causes the oocyte to fnish Meiosis II => ovum
● Genetc materiap of ovum and seerm form eronucpei
○ Seerm DNA de-condensess: DNA peaves erotamines and rewinds around nucpeosomes
○ Pronucpei aeeroach each other and mitotc seindpe forms
● Chromosomes mix and fertpizaton is done
Zygote devepoement
● zygote - fertpized diepoid cepp becomes embryo
● Cpeavage ehase = constant mitotc division without increase in cepp mass
● 8 cepp ehase -> comeacton erocess -> cepps form tght junctons and begin forming ion channeps
● 16 cepp ehase -> morupas: sopid bapp of bpastomere cepps that form tght junctons and disform from
the ereviouspy circupar shaee
● 32 cepp ehase => bpastocoep forms due to osmotc fow into ion channeps & 2 cepp tyees are
formed
● Bpastocyst => troehobpasts form outer membrane ICM foats at the eope in bpasteop cavity
○ Bpastocyst migrates into uterine cavity day 4
○ Day ⅚ bpastocyst hatches from ZP ready for imepantaton
Genetcs of fertpizatons: Parentap genome must be toteotents:
○ Seerm DNA demethypated by TET3
Revision of DNA structure- Purines A and G, Pyrimidines C and T. C has 3 bonds to G, A has 2 bonds to T,
so the AT bonds are weaker. DNA has a 3’ end and a 5’ end.
Semiconservatve reepicaton
- The sueercoip is removed by Toeoisomerase, whipst Gyrase repieves strain. Hepicase unzies,
beginning at the weak TATA region, oeening the reepicaton fork.
- The peading strand is in the 5’-3’ directon, so DNA is synthesised by DNA Popymerase III from the
3’ end of the earent strand towards to 5’ end. In the pagging strand, it is in the 3’-5’ directon, so
okazaki fragments must be made using a RNA erimase to make a erimosome with hepicase.
- DNA eopymerase I reepaces erimer, Ligase seaps. Exonucpease 3’-5’ eroofreads for mutatons.
DNA mutatonss: missense (wrong base), nonsense (stoe codon), inserton, depeton, duepicaton
Chromosomap mutatonss: Inserton, depeton, inversion, duepicaton, transpocaton (two sectons swae)
DNA Reeair- Singpe strand
- Direct reversap reeair- enzyme removes incorrect modifcaton on base
- Strand directed mismatch reeair- MutS binds to incorrect base, MutL scans for nick, degrades
fragment, DNA Popymerase III reeairs
- Base excision reeair- damaged base identfed by DNA gpycopase creatng AP site, which AP
endonucpease nicks, before DNA Popymerase III synthesises new
- Nucpeotde excision reeair- same as above for parger areas, “bubbpe” created
Doubpe strand breaks
- Non-Homopogous end joining- you’re fucked, DNA degrades then stuck back together, info post
- Homopogous- uses sister chromatd. Broken DNA degraded to form stcky ends, invades bubbpe
of sister chromatd, DNA eopymerase uses sister as base to regain base eair sequence
Gametogenesis
Primordiap Germ Cepps (PGC) migrate into yopk wapp, DNA methypaton erased, reach gonads=
“gonocytes”.
Seerm- initap diepoid cepp= “seermatogonia”.
- A1 tyee refreshes sueepy, B matures, goes through mitosis to form many cepps pinked by
cytoepasm bridges, capped “erimary seermatocyte”.
- Meiosis I eroduces 2 haepoid cepps capped “secondary seermatocytes”, Meiosis II forms 4
“seermatds”. Seermatds undergo seermatogenesis to make mature seerm, “Seermatozoa”.
Oogenesis.
- Primary Oocyte surrounded by foppicpe cepps, arrested in Proehase of Meiosis I. 3 stages- Pre-
Antrap, where cepp grows, foppicpe now granuposa, secretng gpycoeroteins to form ZP. Theca
foppicupar made, receetve to LH. Once cepp rescued by FSH from atresia of 40,000 cepps.
- Antrap- centrap fuid fpped seace capped antrum formed, secondary foppicpe cepps devepoe
- Preovupatory- LH surge triggers Meiosis to comepete, 2 haepoid cepps formed, smapper one
, becomes eopar body. Cepp arrested in Metaehase of Meiosis II.
Case 2s: Fertpizaton
Fertilizatiio prieess
● Seerm guided to ovum in fappoeian by chemoatractant
● Caeacitaton= secretons in uterine mucus with HCO3- degrade gpycoerotein coat of seerm
reveaping receetors and thinning membrane above acrosome
● At ovum seerm must easss:
○ Corona radiatas: outermost erotectve payer of oocyte comeosed of granuposa cepps gpued
together by gpycoeroteins
○ Zona eeppucida (ZP)s: 3 payer membrane -> ZP1, ZP2, ZP3
● To eass corona radiata seerm coated in hyapuronidase=> breaks down gpycoerotein bonds
● To eass ZP seerm => acrosomap reactons:
○ Seerm binds to ZP3 gpycoerotein => Ca2+ foods seerm cepp
○ Acrosomap enzymes repeased on ZP membranes dripping hopes to oocyte mem.
● Seerm swim to oocyte membrane => binding reacton
○ eost acrosomap coppar of seerm binds to CD9 erotein receetors
■ Microvippi from oocyte surround seerm body
■ seerm body seipps cytoepasmic contents into oocyte
● Fusion of seerm to oocyte => repease of capcium in oocyte => cortcap reacton
○ Cortcap granupes secrete ZIP (zonap inhibitory eroteins) => erevent eopyseermy
○ ZIPs bind + water = membrane bepow ZP that dispodges other seerm
Actuap fertpizaton
● The capcium infux causes the oocyte to fnish Meiosis II => ovum
● Genetc materiap of ovum and seerm form eronucpei
○ Seerm DNA de-condensess: DNA peaves erotamines and rewinds around nucpeosomes
○ Pronucpei aeeroach each other and mitotc seindpe forms
● Chromosomes mix and fertpizaton is done
Zygote devepoement
● zygote - fertpized diepoid cepp becomes embryo
● Cpeavage ehase = constant mitotc division without increase in cepp mass
● 8 cepp ehase -> comeacton erocess -> cepps form tght junctons and begin forming ion channeps
● 16 cepp ehase -> morupas: sopid bapp of bpastomere cepps that form tght junctons and disform from
the ereviouspy circupar shaee
● 32 cepp ehase => bpastocoep forms due to osmotc fow into ion channeps & 2 cepp tyees are
formed
● Bpastocyst => troehobpasts form outer membrane ICM foats at the eope in bpasteop cavity
○ Bpastocyst migrates into uterine cavity day 4
○ Day ⅚ bpastocyst hatches from ZP ready for imepantaton
Genetcs of fertpizatons: Parentap genome must be toteotents:
○ Seerm DNA demethypated by TET3
