DNA Damage

When is NER used?

large and bulky repair (akylation, thymine dimer, etc)

When are lesions sent?

during trnascription

in NER, endonuclease removes….

the lesion and 30 nucleotides

What comes in and fills the gap after NER?

DNA pol epsilon and omega

What are the major players in GC-NER?

UV-DDB, RAD 238

Whart are the major players in TC NER

CSA, CSB

Which type of NER is UV DDB considered a major palyer?

GC NER

Which type of NER is Rad238 considered a major palyer?

GC NER

Which type of CSA is UV DDB considered a major palyer?

TC NER

Which type of NER is UV DDB considered a major palyer?

GC NER

UV DDB and RAD 238 do what?

sense helix distortion

CSA and CSB are recruited by what?

stalled RNA pol

For NER, what are the main players for both GC and TC NER

TFIIH, ERCC1, PCNA and RPA

What is TFIIH?

large helicase complex

What is ERCC1?

nuclease

Xeroderma Pigmentosum is caused by…

NER

alterations done to a specific nucleotides

Base excision repair

What causes BER

chemical modifications

What is the first step of BER

DBA glycosylase recognizes lesions

What is the second step of BER?

AP endonuclease recognizes lesion and nicks in DNA strand

What is the third step of BER?

DNA polymerase and DNA ligase fill gap

What does DNA glycosylase make in BER?

an apurinic or apyridiminic site

BER mutations are assoicated with…

increased cancer risk

Mismatch repair is used to…

repair errors incorporated during replication that get past proofreading

What errors might go through MR

insertions, deletions

What is tautomerization

conversion of one nitrogenous base into another isomer

How does a cell know when a base is correct (bateria)

the template is marked with methylation

DSB repair occurs due to…

high energy

DSB run a major risk of…

chromosomal translocation and rearrangement

Homologus repair requires ______ to occur

a sister chromatid template

HR can only occur during

S phase or G2

What is the first step of HR

5’ ends are degraded

What is the second step of HR?

3’ overhang finds complementary sequence in sister chromatid

What is the final step of HR

polymerization of original strand using sister chromatid template

What is the complex that recognizes double strand breaks in HR

MRN complex

What comprizes the MRN compelx?

Mre11, Rad51, Nbs1

Rad51 does what?

facilitates search invasion and strand transfer in HR

NHEJ occurs in what pahse?

G1 when no sister chromatid is available

Major players in NHEJ

Ku and DNA PKCs

Is NHEJ perfect?

No, prone to many errors

Ku70 and Ku80 do what?

protect from exonuclease degradation in NHEJ

DKA PKCs are what type of kinase?

S/T kinase

ATM and ATR are what type of kinase?

S/T

ATM and ATR do what?

regulate cel,lular response to DNA damage

What do ATM and ATR phosphorylate?

Chk1 and Chk2

ATR is more involved in….

S phase damage

ATM is more involved in

dsDNA breaks

Ataxa Telanfiectaia is cause by…

ATM mutation

What does Ataxia telangiecista do?

makes you look high and weak to cancer

ATR recruitment to DNA is dependent on…

RPA to make an active ATM dimer

DNA damage in G1 tends to be dependent on…

p53

rapid CORRECTION OF DNA damage in G1 is caused by

direct inhibiton of CDC25, prevents G1 phosphorylation

DELAYED correction of DNA damage in G1 is caused by…

p53/MDM2 interaction, leading to p21 expression

BRCA1 and BRCA2 mutations are the greastest risk for developing…

HBOC

BRCA1 and BRCA2 are what type of inheritance pattern

autosomal dominant

BRCA 1 is a…

e3 ubiqutin ligase

BRCA2 does what?

binds to ssDNA and Rad51

BRCA1 ids involved in….

signalling

BRCA2 is involved in what type of repair

HR